Skip to main content
SpringerLink
Log in

Adhesive Properties of Neutrophils as a Possible Biomarker of Vascular Disease

  • Reference work entry
  • First Online:
Biomarkers in Cardiovascular Disease

  • 1508 Accesses

Abstract

The migration of leukocytes from blood vessels into inflamed tissues is an essential immunity component. Neutrophils are the first leucocytes to arrive at sites of infection or tissue injuries where they exhibit numerous effector functions. Neutrophil recruitment to inflamed vascular endothelium has been described as a multistep process modulated by chemokines, selectins, and integrins that engage in a stepwise manner to initiate intracellular signals and adhesive bond formation. Thus, chemoattractant-triggered inside-out and integrin-initiated outside-in signaling events cooperate concurrently to increase integrin affinity to its ligands and to stabilize and prolong the arrest of circulating neutrophils. This process enables neutrophils to efficiently navigate the journey from the blood stream to inflammatory sites, which is critical for host defense. However, excessive recruitment of activated neutrophils has been observed to sometimes cause local tissue damage and contribute to the development of inflammatory disorders. Therefore, neutrophils have been implicated in the pathogenesis of both acute and chronic vascular inflammatory diseases. Vascular diseases represent major health problems worldwide. Therefore, due to the economic, social, and health impact, early and precise detections of new biomarkers are crucial to identify the exposed population. Accordingly, the present chapter summarizes recent findings in this area. The aims of this review are to focus on new insights of mechanisms that mediate neutrophil transmigration and to evaluate the adhesive properties of neutrophils as potential biomarkers for vascular diseases.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 299.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AMI:

Acute myocardial infarction

CRP:

C-reactive protein

CRP:

C-reactive protein

DVT:

Deep venous thrombosis

END:

Neurological deterioration

ICAM-1:

Intercellular Adhesion Molecule 1

IL-6:

Interleukin-6

IL-8:

Interleukin-8

LFA-1:

Lymphocyte Function-associated Antigen-1 alphaL beta2 integrin

Mac-1:

Macrophage antigen-1 alphaM integrin

PAR:

Protease-activated receptors

PE:

Pulmonary embolism

PSGL-1:

P-selectin glycoprotein ligand-1

RVO:

Residual vein occlusion

SCD:

Sickle cell disease

TF:

Tissue factor

TNF-α:

Tumor necrosis factor- alpha

VCAM-1:

Vascular cell adhesion molecule-1

VLA-4:

Very Late Antigen-4 alpha4 beta1 integrin

VTE:

Venous thromboembolism

WBC:

White blood cell

References

  • Alvaro-González LC, Freijo-Guerrero MM, Sádaba-Garay F. Inflammatory mechanisms, arteriosclerosis and ischemic stroke: clinical data and perspectives. Rev Neurol. 2002;35(5):452–62.

    PubMed  Google Scholar 

  • Arnaout MA, Mahalingam B, Xiong JP. Integrin structure, allostery, and bidirectional signaling. Annu Rev Cell Dev Biol. 2005;21:381–410.

    Article  CAS  PubMed  Google Scholar 

  • Askari JA, Buckley PA, Mould AP, et al. Linking integrin conformation to function. J Cell Sci. 2009;122(Pt 2):165–70.

    Article  CAS  PubMed  Google Scholar 

  • Assis A, Conran N, Canalli AA, et al. Effect of cytokines and chemokines on sickle neutrophil adhesion to fibronectin. Acta Haematol. 2005;113(2):130–6.

    Article  CAS  PubMed  Google Scholar 

  • Bellavite P, Chirumbolo S, Mansoldo C, et al. Simultaneous assay for oxidative metabolism and adhesion of human neutrophils: evidence for correlations and dissociations of the two responses. J Leukoc Biol. 1992;51(4):329–35.

    CAS  PubMed  Google Scholar 

  • Burns JA, Issekutz TB, Yagita H, et al. The alpha 4 beta 1 (very late antigen (VLA)-4, CD49d/CD29) and alpha 5 beta 1 (VLA-5, CD49e/CD29) integrins mediate beta 2 (CD11/CD18) integrin-independent neutrophil recruitment to endotoxin-induced lung inflammation. J Immunol. 2001;166(7):4644–9.

    Article  CAS  PubMed  Google Scholar 

  • Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991;67(6):1033–6.

    Article  CAS  PubMed  Google Scholar 

  • Canalli AA, Franco-Penteado CF, Saad ST, et al. Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation. Haematologica. 2008;93(4):605–9.

    Article  CAS  PubMed  Google Scholar 

  • Canalli AA, Proença RF, Franco-Penteado CF, et al. Participation of Mac-1, LFA-1 and VLA-4 integrins in the in vitro adhesion of sickle cell disease neutrophils to endothelial layers, and reversal of adhesion by simvastatin. Haematologica. 2011;96(4):526–33.

    Article  CAS  PubMed  Google Scholar 

  • Carrier M, Rodger MA, Wells PS, et al. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost. 2011;9(6):1119–25.

    Article  CAS  PubMed  Google Scholar 

  • Chamorro A. Role of inflammation in stroke and atherothrombosis. Cerebrovasc Dis. 2004;17(3):1–5.

    Article  CAS  Google Scholar 

  • Chia S, Nagurney JT, Brown DF, et al. Association of leukocyte and neutrophil counts with infarct size, left ventricular function and outcomes after percutaneous coronary intervention for ST-elevation myocardial infarction. Am J Cardiol. 2009;103(3):333–7.

    Article  CAS  PubMed  Google Scholar 

  • Chiang EY, Frenette PS. Sickle cell vaso-occlusion. Hematol-Oncol Clin North Am. 2005;19:771–84.

    Article  PubMed  Google Scholar 

  • Chigaev A, Sklar LA. Aspects of VLA-4 and LFA-1 regulation that may contribute to rolling and firm adhesion. Front Immunol. 2012;3:242.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chigaev A, Waller A, Amit O, et al. Real-time analysis of conformation-sensitive antibody binding provides new insights into integrin conformational regulation. J Biol Chem. 2009;284(21):14337–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cosmi B, Legnani C, Cini M, et al. d-dimer levels in combination with residual venous obstruction and the risk of recurrence after anticoagulation withdrawal for a first idiopathic deep vein thrombosis. Thromb Haemost. 2005;94(5):969–74.

    CAS  PubMed  Google Scholar 

  • Cosmi B, Legnani C, Iorio A, et al. Residual venous obstruction, alone and in combination with d-dimer, as a risk factor for recurrence after anticoagulation withdrawal following a first idiopathic deep vein thrombosis in the prolong study. Eur J Vasc Endovasc Surg. 2010;39(3):356–65.

    Article  CAS  PubMed  Google Scholar 

  • Cunningham MA, Romas P, Hutchinson P, et al. Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages. Blood. 1999;94(10):3413–20.

    CAS  PubMed  Google Scholar 

  • Fadlon E, Vordermeier S, Pearson TC, et al. Blood polymorphonuclear leukocytes from the majority of sickle cell patients in the crisis phase of the disease show enhanced adhesion to vascular endothelium and increased expression of CD64. Blood. 1998;91(1):266–74.

    CAS  PubMed  Google Scholar 

  • Fisher TC, Meiselmann HJ. Polymorphonuclear leukocytes in ischemic vascular disease. Thromb Res. 1994;74(1):S21–34.

    Article  CAS  PubMed  Google Scholar 

  • Gibson CM, Cannon CP, Daley WL, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93(5):879–88.

    Article  CAS  PubMed  Google Scholar 

  • Ginsberg MH, Partridge A, Shattil SJ. Integrin regulation. Curr Opin Cell Biol. 2005;17(5):509–16.

    Article  CAS  PubMed  Google Scholar 

  • Gonçalves MS, Queiroz IL, Cardoso AS, et al. Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell disease. Braz J Med Biol Res. 2001;34(10):1309–13.

    Article  PubMed  Google Scholar 

  • Han L, Shen X, Pan L, et al. Aminobenzoic acid hydrazide, a myeloperoxidase inhibitor, alters the adhesive properties of neutrophils isolated from acute myocardial infarction patients. Heart Vessels. 2012;27(5):468–74.

    Article  PubMed  Google Scholar 

  • Hogg N, Patzak I, Willenbrock F. The insider’s guide to leukocyte integrin signalling and function. Nat Rev Immunol. 2011;11(6):416–26.

    Article  CAS  PubMed  Google Scholar 

  • Hu P, Luo BH. Integrin bi-directional signaling across the plasma membrane. J Cell Physiol. 2013;228(2):306–12.

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110(6):673–87.

    Article  CAS  PubMed  Google Scholar 

  • Issekutz AC, Nakazato S, Issekutz TB. Differential roles of VLA-4(CD49d/CD29) and LFA-1(CD11a/CD18) integrins and E- and P-selectin during developing and established active or adoptively transferred adjuvant arthritis in the rat. Immunol Cell Biol. 2003;81(5):397–408.

    Article  CAS  PubMed  Google Scholar 

  • Kasschau MR, Barabino GA, Bridges KR, et al. Adhesion of sickle neutrophils and erythrocytes to fibronectin. Blood. 1996;87(2):771–80.

    CAS  PubMed  Google Scholar 

  • Kim JS, Chopp M, Chen H, et al. Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from patients with ischemic stroke and transient ischemic attacks. J Neurol Sci. 1995;128(1):45–50.

    Article  CAS  PubMed  Google Scholar 

  • Kong F, GarcĂ­a AJ, Mould AP, et al. Demonstration of catch bonds between an integrin and its ligand. J Cell Biol. 2009;185(7):1275–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation. 2004;109(22):2698–704.

    Article  PubMed  Google Scholar 

  • Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med. 2010;38(2):S26–34.

    Article  CAS  PubMed  Google Scholar 

  • Ley K, Laudanna C, Cybulsky MI, et al. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7(9):678–89.

    Article  CAS  PubMed  Google Scholar 

  • Ley K. Integration of inflammatory signals by rolling neutrophils. Immunol Rev. 2002;186:8–18.

    Article  CAS  PubMed  Google Scholar 

  • Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–74.

    Article  CAS  PubMed  Google Scholar 

  • Lum AF, Wun T, Staunton D, et al. Inflammatory potential of neutrophils detected in sickle cell disease. Am J Hematol. 2004;76(2):126–33.

    Article  CAS  PubMed  Google Scholar 

  • Luo BH, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu Rev Immunol. 2007;25:619–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma XL, Lefer DJ, Lefer AM, et al. Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesion molecule-1 in myocardial ischemia and reperfusion. Circulation. 1992;86(3):937–46.

    Article  CAS  PubMed  Google Scholar 

  • McEver RP, Cummings RD. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest. 1997;100(11):S97–103.

    CAS  PubMed  Google Scholar 

  • Meisel SR, Shapiro H, Radnay J, et al. Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging. J Am Coll Cardiol. 1998;31(1):120–5.

    Article  CAS  PubMed  Google Scholar 

  • Mihara M, Hashizume M, Yoshida H, et al. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012;122(4):143–59.

    Article  CAS  Google Scholar 

  • Miner JJ, Xia L, Yago T, et al. Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow. Blood. 2008;112(5):2035–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montresor A, Toffali L, Constantin G, et al. Chemokines and the signaling modules regulating integrin affinity. Front Immunol. 2012;3:127.

    Article  PubMed  PubMed Central  Google Scholar 

  • MĂĽgge A, Heistad DD, Padgett RC, et al. Mechanisms of contraction induced by human leukocytes in normal and atherosclerotic arteries. Circ Res. 1991;69(3):871–80.

    Article  PubMed  Google Scholar 

  • Nishida N, Xie C, Shimaoka M, et al. Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity. 2006;25(4):583–94.

    Article  CAS  PubMed  Google Scholar 

  • Njus BH, Chigaev A, Waller A, et al. Conformational mAb as a tool for integrin ligand discovery. Assay Drug Dev Technol. 2009;7(5):507–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okpala I. The intriguing contribution of white blood cells to sickle cell disease - a red cell disorder. Blood Rev. 2004;18(1):65–73.

    Article  PubMed  Google Scholar 

  • Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem. 2008;54(1):24–38.

    Article  CAS  PubMed  Google Scholar 

  • Petri B, Bixel MG. Molecular events during leukocyte diapedesis. FEBS J. 2006;273(19):4399–407.

    Article  CAS  PubMed  Google Scholar 

  • Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012;33(11):571–7.

    Article  CAS  PubMed  Google Scholar 

  • Romano M, Sironi M, Toniatti C, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997;6(3):315–25.

    Article  CAS  PubMed  Google Scholar 

  • Sackett DL, Haynes RB. The architecture of diagnostic research. BMJ. 2002;324(7336):539–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saha P, Humphries J, Modarai B, et al. Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions. Arterioscler Thromb Vasc Biol. 2011;31(3):506–12.

    Article  CAS  PubMed  Google Scholar 

  • Salas A, Shimaoka M, Phan U, et al. Transition from rolling to firm adhesion can be mimicked by extension of integrin alphaLbeta2 in an intermediate affinity state. J Biol Chem. 2006;281(16):10876–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • SchĂĽrpf T, Springer TA. Regulation of integrin affinity on cell surfaces. EMBO J. 2011;30(23):4712–27.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shamri R, Grabovsky V, Gauguet JM, et al. Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat Immunol. 2005;6(5):497–506.

    Article  CAS  PubMed  Google Scholar 

  • Springer TA, Dustin ML. Integrin inside-out signaling and the immunological synapse. Curr Opin Cell Biol. 2012;24(1):107–15.

    Article  CAS  PubMed  Google Scholar 

  • Swirski FK. Inflammation and repair in the ischaemic myocardium. Hamostaseologie. 2014;35(1):34–6.

    Article  PubMed  Google Scholar 

  • Tadokoro S, Shattil SJ, Eto K, et al. Talin binding to integrin beta tails: a final common step in integrin activation. Science. 2003;302(5642):103–6.

    Article  CAS  PubMed  Google Scholar 

  • Takada Y, Ye X, Simon S. The integrins. Genome Biol. 2007;8(5):215.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tosetto A, Iorio A, Marcucci M, et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost. 2012;10(6):1019–25.

    Article  CAS  PubMed  Google Scholar 

  • Tsai NW, Chang WN, Shaw CF, et al. The value of leukocyte adhesion molecules in patients after ischemic stroke. J Neurol. 2009;256(8):1296–302.

    Article  CAS  PubMed  Google Scholar 

  • Turhan A, Weiss LA, Mohandas N, et al. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci U S A. 2002;99(5):3047–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verhovsek M, Douketis JD, Yi Q, et al. Systematic review: d-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med. 2008;149(7):481–90. W94.

    Article  PubMed  Google Scholar 

  • Voisin MB, Nourshargh S. Neutrophil transmigration: emergence of an adhesive cascade within venular walls. J Innate Immun. 2013;5(4):336–47.

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Luo BH. Structural basis of integrin transmembrane activation. J Cell Biochem. 2010;109(3):447–52.

    CAS  PubMed  Google Scholar 

  • Wang W, Zhu J, Springer TA, et al. Tests of integrin transmembrane domain homo-oligomerization during integrin ligand binding and signaling. J Biol Chem. 2011;286(3):1860–7.

    Article  CAS  PubMed  Google Scholar 

  • Woodfin A, Voisin MB, Nourshargh S. Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol. 2010;17(1):9–17.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu DY, Patti-Diaz L, Hill CG. Development and validation of flow cytometry methods for pharmacodynamic clinical biomarkers. Bioanalysis. 2010;2(9):1617–26.

    Article  CAS  PubMed  Google Scholar 

  • Zapponi KC, Mazetto BM, Bittar LF, et al. Increased adhesive properties of neutrophils and inflammatory markers in venous thromboembolism patients with residual vein occlusion and high d-dimer levels. Thromb Res. 2014;133(5):736–42.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hematology and Hemotherapy Center, University of Campinas (UNICAMP), R. Carlos Chagas, 480, 13073-878, Campinas, SĂŁo Paulo, Brazil

    Kiara C. S. Zapponi, Luis F. Bittar, Aline Barnabé, Bruna M. Mazetto, Fernanda D. Santiago-Bassora, Mariane C. Flores-Nascimento, Erich V. De Paula & Joyce M. Annichino-Bizzacchi

  2. Department of Clinical Pathology, University of Campinas (UNICAMP), R. Carlos Chagas, 480, 13073-878, Campinas, SĂŁo Paulo, Brazil

    Fernanda A. Orsi

Authors
  1. Kiara C. S. Zapponi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernanda A. Orsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luis F. Bittar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aline Barnabé
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bruna M. Mazetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fernanda D. Santiago-Bassora
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mariane C. Flores-Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Erich V. De Paula
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joyce M. Annichino-Bizzacchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kiara C. S. Zapponi .

Editor information

Editors and Affiliations

  1. Department of Biomedical Science, Faculty of Science & Technology , University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Department of Nutrition and Dietetics, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Zapponi, K.C.S. et al. (2016). Adhesive Properties of Neutrophils as a Possible Biomarker of Vascular Disease. In: Patel, V., Preedy, V. (eds) Biomarkers in Cardiovascular Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7678-4_24

Download citation

Publish with us

Policies and ethics

Search

Navigation