Skip to main content
SpringerLink
Log in

Pulmonary Endothelial Cell Apoptosis in Emphysema and Acute Lung Injury

  • Chapter
  • First Online:
Molecular and Functional Insights Into the Pulmonary Vasculature

Part of the book series: Advances in Anatomy, Embryology and Cell Biology ((ADVSANAT,volume 228))

Abstract

Apoptosis plays an essential role in homeostasis and pathogenesis of a variety of human diseases. Endothelial cells are exposed to various environmental and internal stress and endothelial apoptosis is a pathophysiological consequence of these stimuli. Pulmonary endothelial cell apoptosis initiates or contributes to progression of a number of lung diseases. This chapter will focus on the current understanding of the role of pulmonary endothelial cell apoptosis in the development of emphysema and acute lung injury (ALI) and the factors controlling pulmonary endothelial life and death.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

AAT:

Alpha1-anti-trypsin

ADA:

Adenosine deaminase

ADP:

Adenosine-5′-diphosphate

APC:

Activated protein C

ARDS:

Acute respiratory distress syndrome

ARs:

Adenosine receptors

ATF6:

Transcription factor 6

ATGs:

Autophagy-related genes

ATP:

Adenosine-5′-triphosphate

BALF:

Broncheoalveolar lavage fluid

CD39:

ecto-5′-nucleotidase

CD73:

ecto-5′-nucleotidase

CHOP:

C/EBP homologous protein

COPD:

Chronic obstructive pulmonary disease

CS:

Cigarette smoke

CSE:

Cigarette smoke extract

DAMPs:

Damage associated molecular patterns

EC:

Endothelial cells

ECM:

Extracellular matrix

eIF2α:

Eukaryotic initiation factor 2α

ENT1/2:

Equilibrative nucleoside transporter 1/2

ER:

Endoplasmic reticulum

FAC:

Focal adhesion complexes

FAK:

Focal adhesion kinase

GSH:

Glutathione

ICMT:

Isoprenylcysteine-O-carboxyl methyltransferase

IRAK-1:

Interleukin (IL)-1 receptor associated kinase

IRE1:

Inositol-requiring enzyme 1

JNK:

c-Jun N-terminal kinase

LPS:

Lipopolysaccharide

MLKL:

Mixed lineage kinase domain-like protein

mTOR:

Mammalian target of rapamycin

MyD88:

Myeloid differentiation factor 88

PERK:

Pancreatic ER kinase like ER kinase

RBC:

Red blood cells

RIPK1/3:

Receptor-interacting protein kinase 1 and 3

ROS:

Reactive oxygen species

S1P:

Sphingosine 1-phosphate

SAH:

S-adenosyl-l-homocysteine

SAHH:

S-adenosyl-l-homocysteine hydrolase

SAM:

S-Adenosyl-l-Methionine

TLRs:

Toll-like receptors

TNF-α:

Tumor necrosis factor-alpha

TRAF-6:

TNF receptor associated factor-6

UPR:

Unfolded protein response

VEGF:

Vascular endothelial growth factor

VEGFR2:

VEGF receptor type 2

References

  • Abadie Y, Bregeon F, Papazian L, Lange F, Chailley-Heu B, Thomas P, Duvaldestin P, Adnot S, Maitre B, Delclaux C (2005) Decreased VEGF concentration in lung tissue and vascular injury during ARDS. Eur Respir J 25(1):139–146

    Article  CAS  PubMed  Google Scholar 

  • Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD (2010) Critical care and the global burden of critical illness in adults. Lancet 376(9749):1339–1346

    Article  PubMed  Google Scholar 

  • Agrimi G, Di Noia MA, Marobbio CM, Fiermonte G, Lasorsa FM, Palmieri F (2004) Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution. Biochem J 379(Pt 1):183–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albertine KH, Soulier MF, Wang Z, Ishizaka A, Hashimoto S, Zimmerman GA, Matthay MA, Ware LB (2002) Fas and fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome. Am J Pathol 161(5):1783–1796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aldonyte R, Hutchinson ET, Jin B, Brantly M, Block E, Patel J, Zhang J (2008) Endothelial alpha-1-antitrypsin attenuates cigarette smoke induced apoptosis in vitro. COPD 5:153–162

    Article  PubMed  Google Scholar 

  • Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338(6):347–354

    Article  CAS  PubMed  Google Scholar 

  • Aoshiba K, Yokohori N, Nagai A (2003) Alveolar wall apoptosis causes lung destruction and emphysematous changes. Am J Respir Cell Mol Biol 28:555–562

    Article  CAS  PubMed  Google Scholar 

  • Archer RG, Pitelka V, Hammond JR (2004) Nucleoside transporter subtype expression and function in rat skeletal muscle microvascular endothelial cells. Br J Pharmacol 143(1):202–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bachofen M, Weibel ER (1977) Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 116(4):589–615

    Article  CAS  PubMed  Google Scholar 

  • Bachofen M, Weibel ER (1982) Structural alterations of lung parenchyma in the adult respiratory distress syndrome. Clin Chest Med 3(1):35–56

    CAS  PubMed  Google Scholar 

  • Bailey SM, Robinson G, Pinner A, Chamlee L, Ulasova E, Pompilius M, Page GP, Chhieng D, Jhala N, Landar A, Kharbanda KK, Ballinger S, Darley-Usmar V (2006) S-adenosylmethionine prevents chronic alcohol-induced mitochondrial dysfunction in the rat liver. Am J Physiol Gastrointest Liver Physiol 291(5):G857–G867

    Article  CAS  PubMed  Google Scholar 

  • Bannerman DD, Goldblum SE (2003) Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis. Am J Physiol Lung Cell Mol Physiol 284(6):L899–L914

    Article  CAS  PubMed  Google Scholar 

  • Bannerman DD, Eiting KT, Winn RK, Harlan JM (2004) FLICE-like inhibitory protein (FLIP) protects against apoptosis and suppresses NF-kappaB activation induced by bacterial lipopolysaccharide. Am J Pathol 165(4):1423–1431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bao XM, Wu CF, Lu GP (2010) Atorvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4 and p38MAPK. Atherosclerosis 210(1):114–121

    Article  CAS  PubMed  Google Scholar 

  • Boivin D, Beliveau R (1995) Subcellular distribution and membrane association of Rho-related small GTP-binding proteins in kidney cortex. Am J Phys 269:F180–F189

    CAS  Google Scholar 

  • Borgas D, Chambers E, Newton J, Ko J, Rivera S, Rounds S, Lu Q (2016) Cigarette smoke disrupted lung endothelial barrier integrity and increased susceptibility to acute lung injury via histone deacetylase 6. Am J Respir Cell Mol Biol 54(5):683–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braren R, Hu H, Kim YH, Beggs HE, Reichardt LF, Wang R (2006) Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation. J Cell Biol 172(1):151–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buregeya E, Fowler RA, Talmor DS, Twagirumugabe T, Kiviri W, Riviello ED (2014) Acute respiratory distress syndrome in the global context. Glob Heart 9(3):289–295

    Article  PubMed  Google Scholar 

  • Calfee CS, Matthay MA, Eisner MD, Benowitz N, Call M, Pittet JF, Cohen MJ (2011) Active and passive cigarette smoking and acute lung injury after severe blunt trauma. Am J Respir Crit Care Med 183(12):1660–1665

    Article  PubMed  PubMed Central  Google Scholar 

  • Capano M, Crompton M (2006) Bax translocates to mitochondria of heart cells during simulated ischaemia: involvement of AMP-activated and p38 mitogen-activated protein kinases. Biochem J 395(1):57–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cederbaum AI (2011) Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and cytochrome P450 2E1-induced liver injury. World J Gastroenterol 16(11):1366–1376

    Article  CAS  Google Scholar 

  • Chapman HA (1999) A Fas pathway to pulmonary fibrosis. J Clin Invest 104:1–2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen GJ, Harvey BK, Shen H, Chou J, Victor A, Wang Y (2006) Activation of adenosine A3 receptors reduces ischemic brain injury in rodents. J Neurosci Res 84(8):1848–1855

    Article  CAS  PubMed  Google Scholar 

  • Chen ZH, Kim HP, Sciurba FC, Lee SJ, Feghali-Bostwick C, Stolz DB, Dhir R, Landreneau RJ, Schuchert MJ, Yousem SA, Nakahira K, Pilewski JM, Lee JS, Zhang Y, Ryter SW, Choi AM (2008) Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease. PLoS One 3(10):e3316

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen ZH, Lam HC, Jin Y, Kim HP, Cao J, Lee SJ, Ifedigbo E, Parameswaran H, Ryter SW, Choi AM (2010) Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema. Proc Natl Acad Sci U S A 107(44):18880–18885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi AM, Ryter SW, Levine B (2013) Autophagy in human health and disease. N Engl J Med 368(7):651–662

    Article  CAS  PubMed  Google Scholar 

  • Clarke S (1992) Protein isoprenylation and methylation at carboxyl terminal cysteine residues. Annu Rev Biochem 61:355–386

    Article  CAS  PubMed  Google Scholar 

  • Damico R, Simms T, Kim BS, Tekeste Z, Amankwan H, Damarla M, Hassoun PM (2011) p53 mediates cigarette smoke-induced apoptosis of pulmonary endothelial cells: inhibitory effects of macrophage migration inhibitor factor. Am J Respir Cell Mol Biol 44(3):323–332

    Article  CAS  PubMed  Google Scholar 

  • Dauphinee SM, Karsan A (2006) Lipopolysaccharide signaling in endothelial cells. Lab Investig 86(1):9–22

    Article  CAS  PubMed  Google Scholar 

  • Dauphinee SM, Voelcker V, Tebaykina Z, Wong F, Karsan A (2011) Heterotrimeric Gi/Go proteins modulate endothelial TLR signaling independent of the MyD88-dependent pathway. Am J Physiol Heart Circ Physiol 301(6):H2246–H2253

    Article  CAS  PubMed  Google Scholar 

  • De Chiara G, Marcocci ME, Torcia M, Lucibello M, Rosini P, Bonini P, Higashimoto Y, Damonte G, Armirotti A, Amodei S, Palamara AT, Russo T, Garaci E, Cozzolino F (2006) Bcl-2 phosphorylation by p38 MAPK: identification of target sites and biologic consequences. J Biol Chem 281(30):21353–21361

    Article  PubMed  CAS  Google Scholar 

  • Desch CE, O’Hara P, Harlan JM (1989) Antilipopolysaccharide factor from horseshoe crab, Tachypleus tridentatus, inhibits lipopolysaccharide activation of cultured human endothelial cells. Infect Immun 57(5):1612–1614

    CAS  PubMed  PubMed Central  Google Scholar 

  • Di Sano F, Ferraro E, Tufi R, Achsel T, Piacentini M, Cecconi F (2006) Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism. J Biol Chem 281(5):2693–2700

    Article  PubMed  CAS  Google Scholar 

  • Diette GB, Accinelli RA, Balmes JR, Buist AS, Checkley W, Garbe P, Hansel NN, Kapil V, Gordon S, Lagat DK, Yip F, Mortimer K, Perez-Padilla R, Roth C, Schwaninger JM, Punturieri A, Kiley J (2012) Obstructive lung disease and exposure to burning biomass fuel in the indoor environment. Glob Heart 7(3):265–270

    Article  PubMed  PubMed Central  Google Scholar 

  • Digaleh H, Kiaei M, Khodagholi F (2013) Nrf2 and Nrf1 signaling and ER stress crosstalk: implication for proteasomal degradation and autophagy. Cell Mol Life Sci 70(24):4681–4694

    Article  CAS  PubMed  Google Scholar 

  • Downey GP, Dong Q, Kruger J, Dedhar S, Cherapanov V (1999) Regulation of neutrophil activation in acute lung injury. Chest 116(1 Suppl):46S–54S

    Article  CAS  PubMed  Google Scholar 

  • Eckle T, Fullbier L, Wehrmann M, Khoury J, Mittelbronn M, Ibla J, Rosenberger P, Eltzschig HK (2007) Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury. J Immunol 178(12):8127–8137

    Article  CAS  PubMed  Google Scholar 

  • Eltzschig HK, Faigle M, Knapp S, Karhausen J, Ibla J, Rosenberger P, Odegard KC, Laussen PC, Thompson LF, Colgan SP (2006) Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26. Blood 108(5):1602–1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farley N, Pedraza-Alva G, Serrano-Gomez D, Nagaleekar V, Aronshtam A, Krahl T, Thornton T, Rincon M (2006) p38 mitogen-activated protein kinase mediates the Fas-induced mitochondrial death pathway in CD8+ T cells. Mol Cell Biol 26(6):2118–2129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feoktistov I, Goldstein AE, Ryzhov S, Zeng D, Belardinelli L, Voyno-Yasenetskaya T, Biaggioni I (2002) Differential expression of adenosine receptors in human endothelial cells: role of A2B receptors in angiogenic factor regulation. Circ Res 90(5):531–538

    Article  CAS  PubMed  Google Scholar 

  • Fleming IN, Elliott CM, Exton JH (1996) Differential translocation of Rho family GTPases by lysophosphatidic acid, endothelin-1, and platelet-derived growth factor. J Biol Chem 271:33067–33073

    Article  CAS  PubMed  Google Scholar 

  • Ford ES, Murphy LB, Khavjou O, Giles WH, Holt JB, Croft JB (2015) Total and state-specific medical and absenteeism costs of COPD among adults aged ≥18 years in the United States for 2010 and projections through 2020. Chest 147(1):31–45

    Article  PubMed  Google Scholar 

  • Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53(4):527–552

    CAS  PubMed  Google Scholar 

  • Fujita M, Kuwano K, Kunitake R, Hagimoto N, Miyazaki H, Kaneko Y, Kawasaki M, Maeyama T, Hara N (1998) Endothelial cell apoptosis in lipopolysaccharide-induced lung injury in mice. Int Arch Allergy Immunol 117(3):202–208

    Article  CAS  PubMed  Google Scholar 

  • Gaipl US, Kuhn A, Sheriff A, Munoz LE, Franz S, Voll RE, Kalden JR, Herrmann M (2006) Clearance of apoptotic cells in human SLE. Curr Dir Autoimmun 9:173–187

    CAS  PubMed  Google Scholar 

  • Gill SE, Taneja R, Rohan M, Wang L, Mehta S (2014) Pulmonary microvascular albumin leak is associated with endothelial cell death in murine sepsis-induced lung injury in vivo. PLoS One 9(2):e88501

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gill SE, Rohan M, Mehta S (2015) Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo. Respir Res 16:109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Giordano RJ, Lahdenranta J, Zhen L, Chukwueke U, Petrache I, Langley RR, Fidler IJ, Pasqualini R, Tuder RM, Arap W (2008) Targeted induction of lung endothelial cell apoptosis causes emphysema-like changes in the mouse. J Biol Chem 283(43):29447–29460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldar S, Khaniani MS, Derakhshan SM, Baradaran B (2015) Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev 16(6):2129–2144

    Article  PubMed  Google Scholar 

  • Groenendyk J, Michalak M (2005) Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol 52:381–395

    CAS  PubMed  Google Scholar 

  • Guan JL, Shalloway D (1992) Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 358(6388):690–692

    Article  CAS  PubMed  Google Scholar 

  • Guan JL, Trevithick JE, Hynes RO (1991) Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein. Cell Regul 2(11):951–964

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gustafsson AB, Gottlieb RA (2008) Recycle or die: the role of autophagy in cardioprotection. J Mol Cell Cardiol 44:654–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrington EO, Lu Q, Rounds S (2007) Endothelial cell apoptosis. In: Endothelial biomedicine. Cambridge Press, Cambridge

    Google Scholar 

  • Hengstermann A, Müller T (2008) Endoplasmic reticulum stress induced by aqueous extracts of cigarette smoke in 3T3 cells activates the unfolded-protein-response-dependent PERK pathway of cell survival. Free Radic Biol Med 44:1097–1107

    Article  CAS  PubMed  Google Scholar 

  • Henriquez M, Armisén R, Stutzin A, Quest AF (2008) Cell death by necrosis, a regulated way to go. Curr Mol Med 8(3):187–206

    Article  CAS  PubMed  Google Scholar 

  • Henson PM, Tuder RM (2008) Apoptosis in the lung: induction, clearance and detection. Am J Physiol Lung Cell Mol Physiol 294:L601–L611

    Article  CAS  PubMed  Google Scholar 

  • Holguin F, Moss I, Brown LA, Guidot DM (1998) Chronic ethanol ingestion impairs alveolar type II cell glutathione homeostasis and function and predisposes to endotoxin-mediated acute edematous lung injury in rats. J Clin Invest 101(4):761–768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hotchkiss RS, Strasser A, McDunn JE, Swanson PE (2009) Cell death. N Engl J Med 361(16):1570–1583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsieh SJ, Zhuo H, Benowitz NL, Thompson BT, Liu KD, Matthay MA, Calfee CS, L. National Heart, N. Blood Institute Acute Respiratory Distress Syndrome (2014) Prevalence and impact of active and passive cigarette smoking in acute respiratory distress syndrome. Crit Care Med 42(9):2058–2068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu X, Yee E, Harlan JM, Wong F, Karsan A (1998) Lipopolysaccharide induces the antiapoptotic molecules, A1 and A20, in microvascular endothelial cells. Blood 92(8):2759–2765

    CAS  PubMed  Google Scholar 

  • Huang D, Khoe M, Befekadu M, Chung S, Takata Y, Ilic D, Bryer-Ash M (2007) Focal adhesion kinase mediates cell survival via NF-kappaB and ERK signaling pathways. Am J Physiol Cell Physiol 292(4):C1339–C1352

    Article  CAS  PubMed  Google Scholar 

  • Hungerford JE, Compton MT, Matter ML, Hoffstrom BG, Otey CA (1996) Inhibition of pp125FAK in cultured fibroblasts results in apoptosis. J Cell Biol 135(5):1383–1390

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69(1):11–25

    Article  CAS  PubMed  Google Scholar 

  • Iizuka T, Ishii Y, Itoh K, Kiwamoto T, Kimura T, Matsuno Y, Morishima Y, Yamamoto M, Sekizawa K (2005) Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema. Genes Cells 10(12):1113–1125

    Article  CAS  PubMed  Google Scholar 

  • Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T (1995) Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377(6549):539–544

    Article  CAS  PubMed  Google Scholar 

  • Ilic D, Almeida EA, Schlaepfer DD, Dazin P, Aizawa S, Damsky CH (1998) Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis. J Cell Biol 143(2):547–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ilic D, Kovacic B, McDonagh S, Jin F, Baumbusch C, Gardner DG, Damsky CH (2003) Focal adhesion kinase is required for blood vessel morphogenesis. Circ Res 92(3):300–307

    Article  CAS  PubMed  Google Scholar 

  • Imai K, Mercer BA, Schulman LL, Sonett JR, D’Armiento JM (2005) Correlation of lung surface area to apoptosis and proliferation in human emphysema. Eur Respir J 25(2):250–258

    Article  CAS  PubMed  Google Scholar 

  • Iribarren C, Jacobs DR Jr, Sidney S, Gross MD, Eisner MD (2000) Cigarette smoking, alcohol consumption, and risk of ARDS: a 15-year cohort study in a managed care setting. Chest 117(1):163–168

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen E, Stinson A, Shan L, Yang J, Gietl D, Albino AP (2008) Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells. BMC Cancer 8:229

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF (2000) Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106:1311–1319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kasahara Y, Tuder RM, Cool CD, Lynch DA, Flores SC, Voelkel NF (2001) Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med 163:737–744

    Article  CAS  PubMed  Google Scholar 

  • Kawasaki M, Kuwano K, Hagimoto N, Matsuba T, Kunitake R, Tanaka T, Maeyama T, Hara N (2000) Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor. Am J Pathol 157(2):597–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelsen SG, Duan X, Ji R, Perez O, Liu C, Merali S (2008) Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach. Am J Respir Cell Mol Biol 38:541–550

    Article  CAS  PubMed  Google Scholar 

  • Kennedy SG, Wagner AJ, Conzen SD, Jordan J, Bellacosa A, Tsichlis PN, Hay N (1997) The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev 11(6):701–713

    Article  CAS  PubMed  Google Scholar 

  • Kerr J, Wyllie A, Currie A (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khaltaev N (2005) WHO strategy for prevention and control of chronic obstructive pulmonary disease. Exp Lung Res 31(Suppl 1):55–56

    PubMed  Google Scholar 

  • Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J (1997) Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J 16(10):2783–2793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SJ, Zhang Z, Hitomi E, Lee YC, Mukherjee AB (2006) Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL. Hum Mol Genet 15(11):1826–1834

    Article  CAS  PubMed  Google Scholar 

  • Kim HP, Wang X, Chen ZH, Lee SJ, Huang MH, Wang Y, Ryter SW, Choi AM (2008) Autophagic proteins regulate cigarette smoke-induced apoptosis: protective role of heme oxygenase-1. Autophagy 4(7):887–895

    Article  CAS  PubMed  Google Scholar 

  • Klionsky DJ et al (2016) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 12(1):1–222

    Article  PubMed  PubMed Central  Google Scholar 

  • Kramer K, Harrington EO, Lu Q, Bellas R, Newton J, Sheahan KL, Rounds S (2003) Isoprenylcysteine carboxyl methyltransferase activity modulates endothelial cell apoptosis. Mol Biol Cell 14(3):848–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kranenburg O, Poland M, Gebbink M, Oomen L, Moolenaar WH (1997) Dissociation of LPA-induced cytoskeletal contraction from stress fiber formation by differential localization of RhoA. J Cell Sci 110:2417–2427

    CAS  PubMed  Google Scholar 

  • LaCasse EC, Baird S, Korneluk RG, MacKenzie AE (1998) The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 17(25):3247–3259

    Article  PubMed  Google Scholar 

  • Li H, Zhu H, Xu C, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas-pathway of apoptosis. Cell 94:491–501

    Article  CAS  PubMed  Google Scholar 

  • Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, Shokat KM, Lavail MM, Walter P (2007) IRE1 signaling affects cell fate during the unfolded protein response. Science 318(5852):944–949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linkermann A, Green DR (2014) Necroptosis. N Engl J Med 370(5):455–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Q (2008) Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5. Am J Physiol Lung Cell Mol Physiol 295(1):L123–L133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Q, Rounds S (2009) Pulmonary endothelial cell death: implications for lung disease pathogenesis. In: Voelkel NF, Rounds S (eds) The pulmonary endothelium: function in health and disease. Wiley, Chichester, pp 243–260

    Google Scholar 

  • Lu Q, Sakhatskyy P, Grinnell K, Newton J, Ortiz M, Wang Y, Sanchez-Esteban J, Harrington EO, Rounds S (2011) Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase. Am J Physiol Lung Cell Mol Physiol 301(6):L847–L857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Q, Newton J, Hsiao V, Shamirian P, Blackburn MR, Pedroza M (2012) Sustained adenosine exposure causes lung endothelial barrier dysfunction via nucleoside transporter-mediated signaling. Am J Respir Cell Mol Biol 47(5):604–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Q, Sakhatskyy P, Newton J, Shamirian P, Hsiao V, Curren S, Gabino Miranda GA, Pedroza M, Blackburn MR, Rounds S (2013) Sustained adenosine exposure causes lung endothelial apoptosis: a possible contributor to cigarette smoke-induced endothelial apoptosis and lung injury. Am J Physiol Lung Cell Mol Physiol 304(5):L361–L370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Machino T, Hashimoto S, Maruoka S, Gon Y, Hayashi S, Mizumura K, Nishitoh H, Ichijo H, Horie T (2003) Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates hydrogen peroxide-induced apoptosis in human pulmonary vascular endothelial cells. Crit Care Med 31(12):2776–2781

    Article  CAS  PubMed  Google Scholar 

  • Martin TR, Pistorese BP, Chi EY, Goodman RB, Matthay MA (1989) Effects of leukotriene B4 in the human lung. Recruitment of neutrophils into the alveolar spaces without a change in protein permeability. J Clin Invest 84(5):1609–1619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin TR, Hagimoto N, Nakamura M, Matute-Bello G (2005) Apoptosis and epithelial injury in the lungs. Proc Am Thorac Soc 2(3):214–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matot I, Weiniger CF, Zeira E, Galun E, Joshi BV, Jacobson KA (2006) A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion. Crit Care 10(2):R65

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsuzawa A, Ichijo H (2008) Redox control of cell fate by MAP kinase: physiological roles of ASK1-MAP kinase pathway in stress signaling. Biochim Biophys Acta 1780(11):1325–1336

    Article  CAS  PubMed  Google Scholar 

  • Matthay MA, Ware LB, Zimmerman GA (2012) The acute respiratory distress syndrome. J Clin Invest 122(8):2731–2740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matute-Bello G, Liles WC, Steinberg KP, Kiener PA, Mongovin S, Chi EY, Jonas M, Martin TR (1999) Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS). J Immunol 163(4):2217–2225

    CAS  PubMed  Google Scholar 

  • Michaelson D, Silletti J, Murphy G, Peter DE, Rush M, Philips MR (2001) Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J Cell Biol 152:111–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizumura K, Cloonan SM, Nakahira K, Bhashyam AR, Cervo M, Kitada T, Glass K, Owen CA, Mahmood A, Washko GR, Hashimoto S, Ryter SW, Choi AM (2014) Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD. J Clin Invest 124(9):3987–4003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizuno S, Yasuo M, Bogaard HJ, Kraskauskas D, Alhussaini A, Gomez-Arroyo J, Farkas D, Farkas L, Voelkel NF (2012) Copper deficiency induced emphysema is associated with focal adhesion kinase inactivation. PLoS One 7(1):e30678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, Dellavalle R, Danaei G, Ezzati M, Fahimi A, Flaxman D, Foreman S, Gabriel E, Gakidou N, Kassebaum S, Khatibzadeh S, Lim S, Lipshultz E, London S, Lopez AD, MacIntyre MF, Mokdad AH, Moran A, Moran AE, Mozaffarian D, Murphy T, Naghavi M, Pope C, Roberts T, Salomon J, Schwebel DC, Shahraz S, Sleet DA, Murray CJ, Abraham J, Ali MK, Atkinson C, Bartels DH, Bhalla K, Birbeck G, Burstein R, Chen H, Criqui MH, Dahodwala N, Jarlais DC, Ding EL, Dorsey ER, Ebel BE, Ezzati M, Fahami SF, Flaxman AD, Gonzalez-Medina D, Grant B, Hagan H, Hoffman H, Kassebaum N, Khatibzadeh S, Leasher JL, Lin J, Lipshultz SE, Lozano R, Lu Y, Mallinger L, McDermott MM, Micha R, Miller TR, Mokdad AA, Mokdad AH, Mozaffarian D, Naghavi M, Narayan KM, Omer SB, Pelizzari PM, Phillips D, Ranganathan D, Rivara FP, Roberts T, Sampson U, Sanman E, Sapkota A, Schwebel DC, Sharaz S, Shivakoti R, Singh GM, Singh D, Tavakkoli M, Towbin JA, Wilkinson JD, Zabetian A, Murray CJ, Abraham J, Ali MK, Alvardo M, Atkinson C, Baddour LM, Benjamin EJ, Bhalla K, Birbeck G, Bolliger I, Burstein R, Carnahan E, Chou D, Chugh SS, Cohen A, Colson KE, Cooper LT, Couser W, Criqui MH, Dabhadkar KC, Dellavalle RP, Jarlais DC, Dicker D, Dorsey ER, Duber H, Ebel BE, Engell RE, Ezzati M, Felson DT, Finucane MM, Flaxman S, Flaxman AD, Fleming T, Foreman K, Forouzanfar MH, Freedman G, Freeman MK, Gakidou E, Gillum RF, Gonzalez-Medina D, Gosselin R, Gutierrez HR, Hagan H, Havmoeller R, Hoffman H, Jacobsen KH, James SL, Jasrasaria R, Jayarman S, Johns N, Kassebaum N, Khatibzadeh S, Lan Q, Leasher JL, Lim S, Lipshultz SE, London S, Lopez AD, Lozano R, Lu Y, Mallinger L, Meltzer M, Mensah GA, Michaud C, Miller TR, Mock C, Moffitt TE, Mokdad AA, Mokdad AH, Moran A, Naghavi M, Narayan KM, Nelson RG, Olives C, Omer SB, Ortblad K, Ostro B, Pelizzari PM, Phillips D, Raju M, Razavi H, Ritz B, Roberts T, Sacco RL, Salomon J, Sampson U, Schwebel DC, Shahraz S, Shibuya K, Silberberg D, Singh JA, Steenland K, Taylor JA, Thurston GD, Vavilala MS, Vos T, Wagner GR, Weinstock MA, Weisskopf MG, Wulf S, Murray CJ, U. S. B. o. D. Collaborators (2013) The state of US health, 1990–2010: burden of diseases, injuries, and risk factors. JAMA 310(6):591–608

    Article  CAS  PubMed  Google Scholar 

  • No Authors (1997) Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ 75(5):397–415

    Google Scholar 

  • Noguchi T, Ishii K, Fukutomi H, Naguro I, Matsuzawa A, Takeda K, Ichijo H (2008) Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAPK pathway for extracellular ATP-induced apoptosis in macrophage. J Biol Chem 283(12):7657–7665

    Article  CAS  PubMed  Google Scholar 

  • Obeng EA, Boise LH (2005) Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis. J Biol Chem 280(33):29578–29587

    Article  CAS  PubMed  Google Scholar 

  • Ola MS, Nawaz M, Ahsan H (2011) Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 351(1–2):41–58

    Article  CAS  PubMed  Google Scholar 

  • Olson M, Kornbluth S (2001) Mitochondria in apoptosis and human disease. Curr Mol Med 1(1):91–122

    Article  CAS  PubMed  Google Scholar 

  • Parsons JT (2003) Focal adhesion kinase: the first ten years. J Cell Sci 116(Pt 8):1409–1416

    Article  CAS  PubMed  Google Scholar 

  • Pastor LM, Sánchez-Gascón F, Girona JC, Bernal-Mañas CM, Morales E, Beltrán-Frutos E, Canteras M (2006) Morphogenesis of rat experimental pulmonary emphysema induced by intratracheally administered papain: changes in elastic fibres. Histol Histopathol 21(12):1309–1319

    CAS  PubMed  Google Scholar 

  • Perl M, Chung CS, Lomas-Neira J, Rachel TM, Biffl WL, Cioffi WG, Ayala A (2005) Silencing of Fas, but not caspase-8, in lung epithelial cells ameliorates pulmonary apoptosis, inflammation, and neutrophil influx after hemorrhagic shock and sepsis. Am J Pathol 167(6):1545–1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perl M, Chung CS, Perl U, Lomas-Neira J, de Paepe M, Cioffi WG, Ayala A (2007) Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury. Am J Respir Crit Care Med 176(6):591–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perl M, Lomas-Neira J, Venet F, Chung CS, Ayala A (2011) Pathogenesis of indirect (secondary) acute lung injury. Expert Rev Respir Med 5(1):115–126

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrache I, Natarajan V, Zhen L, Medler TR, Richter AT, Cho C, Hubbard WC, Berdyshev EV, Tuder RM (2005) Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nat Med 11:491–498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrache I, Fijalkowska I, Medler TR, Skirball J, Cruz P, Zhen L, Petrache HI, Flotte TR, Tuder RM (2006) Alpha-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis. Am J Pathol 169:1155–1166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pittet JF, Mackersie RC, Martin TR, Matthay MA (1997) Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 155(4):1187–1205

    Article  CAS  PubMed  Google Scholar 

  • Qing DY, Conegliano D, Shashaty MG, Seo J, Reilly JP, Worthen GS, Huh D, Meyer NJ, Mangalmurti NS (2014) Red blood cells induce necroptosis of lung endothelial cells and increase susceptibility to lung inflammation. Am J Respir Crit Care Med 190(11):1243–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reytor E, Perez-Miguelsanz J, Alvarez L, Perez-Sala D, Pajares MA (2009) Conformational signals in the C-terminal domain of methionine adenosyltransferase I/III determine its nucleocytoplasmic distribution. FASEB J 23(10):3347–3360

    Article  CAS  PubMed  Google Scholar 

  • Rivo J, Zeira E, Galun E, Matot I (2004) Activation of A3 adenosine receptor provides lung protection against ischemia-reperfusion injury associated with reduction in apoptosis. Am J Transplant 4(12):1941–1948

    Article  CAS  PubMed  Google Scholar 

  • Rounds S, Yee WL, Dawicki DD, Harrington E, Parks N, Cutaia MV (1998) Mechanism of extracellular ATP- and adenosine-induced apoptosis of cultured pulmonary artery endothelial cells. Am J Phys 275(2 Pt 1):L379–L388

    CAS  Google Scholar 

  • Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353(16):1685–1693

    Article  CAS  PubMed  Google Scholar 

  • Ruchko M, Gorodnya O, LeDoux SP, Alexeyev MF, Al-Mehdi AB, Gillespie MN (2005) Mitochondrial DNA damage triggers mitochondrial dysfunction and apoptosis in oxidant-challenged lung endothelial cells. Am J Physiol Lung Cell Mol Physiol 288(3):L530–L535

    Article  CAS  PubMed  Google Scholar 

  • Rutkowski DT, Arnold SM, Miller CN, Wu J, Li J, Gunnison KM, Mori K, Sadighi Akha AA, Raden D, Kaufman RJ (2006) Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol 4(11):e374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sakhatskyy P, Gabino Miranda GA, Newton J, Lee CG, Choudhary G, Vang A, Rounds S, Lu Q (2014) Cigarette smoke-induced lung endothelial apoptosis and emphysema are associated with impairment of FAK and eIF2alpha. Microvasc Res 94:80–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandford AJ, Weir TD, Pare PD (1997) Genetic risk factors for chronic obstructive pulmonary disease. Eur Respir J 10(6):1380–1391

    Article  CAS  PubMed  Google Scholar 

  • Sata M, Takabatake N, Inoue S, Shibata Y, Abe S, Machiya J, Wada T, Ji G, Kido T, Matsuura T, Muramatsu MA, Kubota I (2007) Intronic single-nucleotide polymorphisms in Bcl-2 are associated with chronic obstructive pulmonary disease severity. Respirology 12:34–41

    Article  PubMed  Google Scholar 

  • Savill J, Dransfield I, Gregory C, Haslett C (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2(12):965–975

    Article  CAS  PubMed  Google Scholar 

  • Schaller MD, Hildebrand JD, Shannon JD, Fox JW, Vines RR, Parsons JT (1994) Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol 14(3):1680–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schroder M, Kaufman RJ (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789

    Article  PubMed  CAS  Google Scholar 

  • Shapiro SD (1995) The pathogenesis of emphysema: the elastase:antielastase hypothesis 30 years later. Proc Assoc Am Physicians 107(3):346–352

    CAS  PubMed  Google Scholar 

  • Shapiro SD (1999) The macrophage in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 160(5 Pt 2):S29–S32

    Article  CAS  PubMed  Google Scholar 

  • Shapiro SD, Goldstein NM, Houghton AM, Kobayashi DK, Kelley D, Belaaouaj A (2003) Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol 163(6):2329–2335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen TL, Park AY, Alcaraz A, Peng X, Jang I, Koni P, Flavell RA, Gu H, Guan JL (2005) Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol 169(6):941–952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simonis G, Wiedemann S, Joachim D, Weinbrenner C, Marquetant R, Strasser RH (2009) Stimulation of adenosine A2b receptors blocks apoptosis in the non-infarcted myocardium even when administered after the onset of infarction. Mol Cell Biochem 328(1-2):119–126

    Article  CAS  PubMed  Google Scholar 

  • Sipkens JA, Hahn NE, Blom HJ, Lougheed SM, Stehouwer CD, Rauwerda JA, Krijnen PA, van Hinsbergh VW, Niessen HW (2012) S-Adenosylhomocysteine induces apoptosis and phosphatidylserine exposure in endothelial cells independent of homocysteine. Atherosclerosis 221(1):48–54

    Article  CAS  PubMed  Google Scholar 

  • Steinberg KP, Milberg JA, Martin TR, Maunder RJ, Cockrill BA, Hudson LD (1994) Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome. Am J Respir Crit Care Med 150(1):113–122

    Article  CAS  PubMed  Google Scholar 

  • Subramanian S, Steer CJ (2010) MicroRNAs as gatekeepers of apoptosis. J Cell Physiol 223(2):289–298

    CAS  PubMed  Google Scholar 

  • Surolia R, Karki S, Kim H, Yu Z, Kulkarni T, Mirov SB, Carter AB, Rowe SM, Matalon S, Thannickal VJ, Agarwal A, Antony VB (2015) Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice. Am J Physiol Lung Cell Mol Physiol 309(3):L280–L292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szegezdi E, Fitzgerald U, Samali A (2003) Caspase-12 and ER-stress-mediated apoptosis: the story so far. Ann N Y Acad Sci 1010:186–194

    Article  CAS  PubMed  Google Scholar 

  • Szegezdi E, Logue SE, Gorman AM, Samali A (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7(9):880–885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang K, Rossiter HB, Wagner PD, Breen EC (2004) Lung-targeted VEGF inactivation leads to an emphysema phenotype in mice. J Appl Physiol 97:1559–1566

    Article  CAS  PubMed  Google Scholar 

  • Taraseviciene-Stewart L, Voelkel NF (2008) Molecular pathogenesis of emphysema. J Clin Invest 118(2):394–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson LF, Eltzschig HK, Ibla JC, Van De Wiele CJ, Resta R, Morote-Garcia JC, Colgan SP (2004) Crucial role for ecto-5′-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200(11):1395–1405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorburn A (2004) Death receptor-induced cell killing. Cell Signal 16(2):139–144

    Article  CAS  PubMed  Google Scholar 

  • Tuder RM, Wood K, Taraseviciene L, Flores SC, Voekel NF (2000) Cigarette smoke extract decreases the expression of vascular endothelial growth factor by cultured cells and triggers apoptosis of pulmonary endothelial cells. Chest 117(5 Suppl 1):241S–242S

    Article  CAS  PubMed  Google Scholar 

  • Umapathy NS, Fan Z, Zemskov EA, Alieva IB, Black SM, Verin AD (2010) Molecular mechanisms involved in adenosine-induced endothelial cell barrier enhancement. Vasc Pharmacol 52(5–6):199–206

    Article  CAS  Google Scholar 

  • Villar J, Kacmarek RM, Perez-Mendez L, Aguirre-Jaime A (2006) A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 34(5):1311–1318

    Article  PubMed  Google Scholar 

  • Voelkel NF, Vandivier RW, Tuder RM (2006) Vascular endothelial growth factor in the lung. Am J Physiol Lung Cell Mol Physiol 290:L209–L221

    Article  CAS  PubMed  Google Scholar 

  • Volmer JB, Thompson LF, Blackburn MR (2006) Ecto-5′-nucleotidase (CD73)-mediated adenosine production is tissue protective in a model of bleomycin-induced lung injury. J Immunol 176(7):4449–4458

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412(6844):346–351

    Article  CAS  PubMed  Google Scholar 

  • Wang HL, Akinci IO, Baker CM, Urich D, Bellmeyer A, Jain M, Chandel NS, Mutlu GM, Budinger GR (2007) The intrinsic apoptotic pathway is required for lipopolysaccharide-induced lung endothelial cell death. J Immunol 179(3):1834–1841

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Cui L, Joseph J, Jiang B, Pimental D, Handy DE, Liao R, Loscalzo J (2011) Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress. J Mol Cell Cardiol 52(3):753–760

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wheaton AG, Cunningham TJ, Ford ES, Croft JB, C. Centers for Disease and Prevention (2015) Employment and activity limitations among adults with chronic obstructive pulmonary disease–United States, 2013. MMWR Morb Mortal Wkly Rep 64(11):289–295

    PubMed  Google Scholar 

  • Wyatt AW, Steinert JR, Wheeler-Jones CP, Morgan AJ, Sugden D, Pearson JD, Sobrevia L, Mann GE (2002) Early activation of the p42/p44MAPK pathway mediates adenosine-induced nitric oxide production in human endothelial cells: a novel calcium-insensitive mechanism. FASEB J 16(12):1584–1594

    Article  CAS  PubMed  Google Scholar 

  • Yakes FM, Van Houten B (1997) Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci U S A 94(2):514–519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zen K, Karsan A, Stempien-Otero A, Yee E, Tupper J, Li X, Eunson T, Kay MA, Wilson CB, Winn RK, Harlan JM (1999) NF-kappaB activation is required for human endothelial survival during exposure to tumor necrosis factor-alpha but not to interleukin-1beta or lipopolysaccharide. J Biol Chem 274(40):28808–28815

    Article  CAS  PubMed  Google Scholar 

  • Zhande R, Dauphinee SM, Thomas JA, Yamamoto M, Akira S, Karsan A (2007) FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. Mol Cell Biol 27(21):7394–7404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Mohsenin A, Morschl E, Young HW, Molina JG, Ma W, Sun CX, Martinez-Valdez H, Blackburn MR (2009) Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor. J Immunol 182(12):8037–8046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Murthy JN, Zeng D, Belardinelli L, Blackburn MR (2010) Alterations in adenosine metabolism and signaling in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. PLoS One 5(2):e9224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported with the use of facilities at the Providence VA Medical Center and by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103652 (Lu, project 1), P20GM103652 (Rounds), VA Merit Review (Rounds), NIH Ro1 HL130230 (Lu).

Author information

Authors and Affiliations

  1. Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA

    Eboni Chambers, Sharon Rounds & Qing Lu

  2. Vascular Research Laboratory, Providence Veterans Affairs Medical Center, Providence, RI, USA

    Eboni Chambers, Sharon Rounds & Qing Lu

Authors
  1. Eboni Chambers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon Rounds
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing Lu .

Editor information

Editors and Affiliations

  1. Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Kaushik Parthasarathi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chambers, E., Rounds, S., Lu, Q. (2018). Pulmonary Endothelial Cell Apoptosis in Emphysema and Acute Lung Injury. In: Parthasarathi, K. (eds) Molecular and Functional Insights Into the Pulmonary Vasculature. Advances in Anatomy, Embryology and Cell Biology, vol 228. Springer, Cham. https://doi.org/10.1007/978-3-319-68483-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-68483-3_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-68482-6

  • Online ISBN: 978-3-319-68483-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation