• Armando E. Fraire
Part of the Molecular Pathology Library book series (MPLB, volume 1)


In the lung, as in other anatomic sites, inflammation can be regarded as a complex, generally salutary response of the body to injurious agents. This bodily response derives from a series of interconnected cellular and molecular events acting in concert with an equally complex array of neurogenic1,2 and vasogenic factors.3, 4, 5 Principal cellular actors playing a role in the inflammatory process include polymorphonuclear leukocytes, lymphocytes, plasma cells, eosinophils, mast cells, monocytes, and macrophages. Leading molecular compounds regulating cellular responses are chemical mediators such as vasoactive amines, prostaglandins, and leukotrienes, as well as members of the kinin and complement activation system (Table 43.1).6 This chapter discusses the major forms of the inflammatory response, namely, acute and chronic inflammation, and addresses granulomatous inflammation. In addition, it covers mechanisms of response selection, innate immunity (Toll receptors), and specific cellular constituents, in particular, pulmonary alveolar macrophages and dendritic cells and their roles in antigen presentation and human leukocyte antigen (HLA)-linked diseases.
Table 43.1

Inflammatory mediators.


Human Leukocyte Antigen Alveolar Macrophage Interstitial Lung Disease Human Leukocyte Antigen Class Hypersensitivity Pneumonitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Tracey KJ. The inflammatory reflex. Nature 2002;420:853–859.CrossRefPubMedGoogle Scholar
  2. 2.
    Richardson JD, Vasko MR. Cellular mechanisms of neurogenic inflammation. Pharmacol Exp Ther 2002;302:839–845.CrossRefGoogle Scholar
  3. 3.
    Majno G, Palade GE. Studies on inflammation. I. The effect of histamine and serotonin on vascular permeability: an electron microscopic study. J Biophys Biochem Cytol 1961;11:571–596.CrossRefPubMedGoogle Scholar
  4. 4.
    Majno G, Palade GE, Schoefl GI. Studies on inflammation. II. The site of action of histamine and serotonin along the vascular tree: a topographic study. J Biophys Biochem Cytol 1961;11:607–626.CrossRefPubMedGoogle Scholar
  5. 5.
    Majno G. Commentary. Chronic inflammation: links with angiogenesis and wound healing. Am J Pathol 1998;153:1035–1039.PubMedGoogle Scholar
  6. 6.
    Kunkel SL, Strieter RM. Cytokines and chemokines in lung inflammation and injury. In Fishman AP, ed. Fishman’s Pulmonary Diseases and Disorders, 3rd ed, vol 1. New York: McGraw-Hill; 1998:315–324.Google Scholar
  7. 7.
    Muller WA. Leukocyte-endothelial cell interactions in the inflammatory response. Lab Invest 2002;82:521–534.CrossRefPubMedGoogle Scholar
  8. 8.
    Kumar V, Abbas AK, Fausto N, ed. Robbins and Cotran Pathologic Basis of Disease, 7th ed. Philadelphia: Elsevier, 2005:47–86.Google Scholar
  9. 9.
    Reynolds HY, Elias JA. Pulmonary defense mechanisms against infections. In Fishman AP, ed. Pulmonary Diseases and Disorders, 3rd ed, vol 1. New York: McGraw-Hill; 1998:265–274.Google Scholar
  10. 10.
    Berman JS, Center DM. Lymphocyte-and macrophage-mediated inflammation in the lung. In Fishman AP, ed. Pulmonary Diseases and Disorders, 3rd ed, vol 1. New York: McGraw-Hill; 1998:275–287.Google Scholar
  11. 11.
    Inlay M. A response to Chapter 6 of Darwin’s Black Box., June 2002.Google Scholar
  12. 12.
    Goldsby RA, Kindt TJ, Osborne BA, et al. Immunology, 5th ed. New York: W.H. Freeman; 2003:69.Google Scholar
  13. 13.
    Collins German Concise Dictionary, 3rd ed. Glasgow, Scotland: Harper Collins, 2006:333.Google Scholar
  14. 14.
    Goldstein DR. Toll like receptors and other links between innate and acquired alloimmunity. Curr Opin Immunol 2004;16:538–544.CrossRefPubMedGoogle Scholar
  15. 15.
    Luke AJ, O’Neill LA. Immunity’s early-warning system. Sci Am 2005;292:38–45.Google Scholar
  16. 16.
    Dunne A, O’Neill LA. The interleukin-1 receptor/Toll like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2003;171:R–3.Google Scholar
  17. 17.
    Lazarus R, Ruby BA, Louge C, et al. Toll-like receptor 10 genetic variation is associated with asthma in two independent samples. Am J Respir Crit Care Med 2004;170:594–600.CrossRefPubMedGoogle Scholar
  18. 18.
    Basu S, Fenton MJ. Toll-like receptors: function and roles in lung disease. Am J Physiol Lung Cell Mol Physiol 2004;286:L887–L892.CrossRefPubMedGoogle Scholar
  19. 19.
    Pons J, Sauleda J, Regueriro V, et al. Expression of toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease. Respir Res 2006;7:64A.CrossRefGoogle Scholar
  20. 20.
    Velasco G, Campo M, Manrique OJ, et al. Toll-like receptor 4 or 2 agonists decrease allergic inflammation. Am J Respir Cell Mol Biol 2005;32:218–224.CrossRefPubMedGoogle Scholar
  21. 21.
    Chen W, Kuo Lee R, Shen H, et al. Toll-like receptor 4 (TLR 4) does not confer a resistance advantage on mice against low-dose aerosol infection with virulent type A Francisella tularensis. Microb Pathog 2004;37:185–191.CrossRefPubMedGoogle Scholar
  22. 22.
    Knapp S, Wieland CW, Florquin S, et al. Differential roles of CD14 and Toll-like receptors 4 and 2 in murine Acinetobacter pneumoniae. Am J Respir Crit Care Med 2006;173:122–129.CrossRefPubMedGoogle Scholar
  23. 23.
    Corrin B, Nicholson AG. Pathology of the Lungs, 2nd ed. Philadelphia: Churchill Livingstone; 2006:1–34.Google Scholar
  24. 24.
    Fujii T, Hayashi S, Hogg JC, et al. Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow. Am J Respir Cell Mol Biol 2002;27:34–41.PubMedGoogle Scholar
  25. 25.
    Abbas AK, Lichtman AH, Pober JS. Cellular and Molecular Immunology, 4th ed. Philadelphia: W.B. Saunders; 2000:22–24.Google Scholar
  26. 26.
    Steinman R, Cohn Z. Identification of a novel cell type in peripheral lymphoid organs of mice. J Exp Med 1973;137:1142–1162.CrossRefPubMedGoogle Scholar
  27. 27.
    Satthaporn S, Eremin O. Dendritic cells (1): Biological functions. J R Coll Surg Edinb 2001;46:9–20.PubMedGoogle Scholar
  28. 28.
    Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245–252.CrossRefPubMedGoogle Scholar
  29. 29.
    Holt PG. Antigen presentation in the lung. Am J Respir Crit Care Med 2000;162:S151–S156.PubMedGoogle Scholar
  30. 30.
    Randolph GJ, Beaulieu S, Lebecque S, et al. Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 1998;282:480–483.CrossRefPubMedGoogle Scholar
  31. 31.
    Godthelp T, Fokkens WJ, Kleinjan A, et al. Antigen presenting cells in the nasal mucosa of patients with allergic rhinitis during allergen provocation. Clin Exp Allergy 1996;26:677–688.CrossRefPubMedGoogle Scholar
  32. 32.
    Fokkens WJ, Vroom M, Rijntjes E, et al. Fluctuation of the number of CD-1 (T6)-positive dendritic cells, presumably Langerhans cells, in the nasal mucosa of patients with an isolated grass-pollen allergy before, during, and after the grass-pollen season. J Allergy Clin Immunol 1989;84:39–43.CrossRefPubMedGoogle Scholar
  33. 33.
    Tunon-de-Lara JM, Redington P, Bradding MK, et al. Dendritic cells in normal and asthmatic airways: expression of the á subunit of the high affinity immunoglobulin E receptor (Fcε RI-α). Clin Exp Allergy 1996;26:648–655CrossRefPubMedGoogle Scholar
  34. 34.
    Majno G, Joris I. Cells, Tissues and Disease. Principles of General Pathology, 2nd ed. New York: Oxford University Press; 2004:442–476.Google Scholar
  35. 35.
    Sharma OP. Clinical diagnosis and types of granulomas. In: Cagle PT, ed. Diagnostic Pulmonary Pathology. New York: Marcel-Dekker; 2000:331–347.Google Scholar
  36. 36.
    Mohan H, ed. Textbook of Pathology, 5th ed. New Delhi: Jaypee Brothers, 2005:153–154.Google Scholar
  37. 37.
    Hasleton PS, ed. Spencer’s Pathology of the Lung, 5th Ed. New York: McGraw-Hill; 1996:1–44.Google Scholar
  38. 38.
    Laga AC, Allen T, Cagle PT. Usual interstitial pneumonia. In: Cagle PT, ed. Color Atlas and Text of Pulmonary Pathology. Philadelphia: Lippincott Williams & Wilkins; 2005:427–429.Google Scholar
  39. 39.
    Laga A, Allen T, Cagle PT. Non specific interstitial pneumonia. In: Cagle PT, ed. Color Atlas and Text of Pulmonary Pathology. Philadelphia: Lippincott Williams & Wilkins, 2005:431–432.Google Scholar
  40. 40.
    Laga A, Allen T, Cagle PT. Cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia). In Cagle PT, ed. Color Atlas and Text of Pulmonary Pathology. Philadelphia: Lippincott Williams & Wilkins; 2005:433–434.Google Scholar
  41. 41.
    Noble PN. Idiopathic pulmonary fibrosis: new insight into classification and pathogenesis usher in a new era in therapeutic approaches. Am J Respir Cell Mol Biol 2003;29:S27–S31.PubMedGoogle Scholar
  42. 42.
    Merrill WW, Reynolds HY. Bronchial lavage in inflammatory lung disease. Clin Chest Med 1983;4:71–84.PubMedGoogle Scholar
  43. 43.
    Wardlaw A. Immunologic basis of lung disease. In Wardlaw AJ, Hamid Q, eds. Textbook of Respiratory Cell and Molecular Biology. London: Martin Dunitz LTD; 2002:47–71.Google Scholar
  44. 44.
    Schubert MS. A superantigen hypothesis for the pathogenesis of chronic hypertrophic rhinosinusitis, allergic fungal sinusitis and related disorders. Ann Allergy Asthma Immunol 2001;87:181–188.CrossRefPubMedGoogle Scholar
  45. 45.
    Kappler, J, Kotzin, B, Herron L, et al. Vβ-specific stimulation of human T cells by staphylococcal toxins. Science 1989:244;811–813.CrossRefPubMedGoogle Scholar
  46. 46.
    Kotb M, Norrby-Teglund A, McGeer A, et al. An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nat Med 2002;8:1398–1404.CrossRefPubMedGoogle Scholar
  47. 47.
    Krakauer T. Immune response to staphylococcal superantigens. Immunol Res 1999;20:163–173.CrossRefPubMedGoogle Scholar
  48. 48.
    Paliard X, West SG, Lafferty JA, et al. Evidence for the effects of a super antigen in rheumatoid arthritis. Science 1991;253:325–329.CrossRefPubMedGoogle Scholar
  49. 49.
    Hauk PJ, Wenzel SE, Trumble AE, et al. Increased T-cell receptor Vβ8+T cells in bronchoalveolar lavage fluid of subjects with poorly controlled asthma: a potential role for microbial superantigens. J Allergy Clin Immunol 1999;103:37–45.CrossRefGoogle Scholar
  50. 50.
    Rammes A, Roth J, Goebeler M, et al. Myeloid-related protein (MRP) 8 and MRP14 calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. J Biol Chem 1997;272:9496–9502.CrossRefPubMedGoogle Scholar
  51. 51.
    Bühling F, Ittenson A, Kaiser D, et al. MRP8 / MRP14, CD11b and HLA-DR expression of alveolar macrophages in pneumonia. Immunol Lett 2000;71:185–190.CrossRefPubMedGoogle Scholar
  52. 52.
    Nishimura M, Mitsunaga S, Ishikawa Y, et al. Possible mechanisms underlying development of transfusion related acute lung injury: roles of anti-major histocompatibility complex class II DR antibodies. Transfusion Med 2003;13:141–147.CrossRefGoogle Scholar
  53. 53.
    Schulman LL, Weinberg AD, McGregor CC, et al. Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation. Am J Respir Crit Care Med 2001;163:437–442.PubMedGoogle Scholar
  54. 54.
    Chalermskulrat W, Neuringer IP, Schmitz JL, et al. Human leukocyte antigen mismatches predispose to the severity of bronchiolitis obliterans syndrome after lung transplantation. Chest 2003;123:1825–1831.CrossRefPubMedGoogle Scholar
  55. 55.
    Hoffman JA, Weinberg RI, Azen CG, et al. Human leukocyte antigen-DR expression on peripheral blood monocytes and the risk of pneumonia in pediatric lung transplant recipients. Transplant Infect Dis 2004;6:147–155.CrossRefGoogle Scholar
  56. 56.
    Muehlstedt SO, Lyte M, Rodriguez JL. Increased IL-10 production and HLA-DR suppression in the lungs of injured patients precede the development of nosocomial pneumonia. Shock 2002;17:443–450.CrossRefPubMedGoogle Scholar
  57. 57.
    Ye Q, Finn PW, Sweeney R, et al. MCH class II-associated invariant chain isoforms regulate pulmonary immune responses. J Immunol 2003;170:1473–1480.PubMedGoogle Scholar
  58. 58.
    Tsybalova LM, Popova TL, Karpukhin GI. HLA system antigens in persons with differing susceptibilities to the causative agents of acute respiratory diseases. Zh Mikrobiol Epidemiol Immunobiol 1989;10:64–68.PubMedGoogle Scholar
  59. 59.
    Selman LM, Chapela R, Salas J, et al. Hypersensitivity pneumonitis: clinical approach and an integral concept about its pathogenesis. A Mexican point of view. In Selman-Lama M, Barrios R, eds. Interstitial Pulmonary Diseases: Selected Topics. Boston: CRC Press; 1991:171–195.Google Scholar
  60. 60.
    Wilson BD, Sternick JL, Yoshizawa Y, et al. Experimental murine hypersensitivity pneumonitis: multigenic control and influence by genes within the I-B subregion of the H-2 complex. J Immunol 1982;129:2160–2163.PubMedGoogle Scholar
  61. 61.
    Rittner G, Sennenkamp J, Mollenhauer E, et al. Pigeons breeder’s lung association with HLA-DR3. Tissue Antigens 1983;21:374–379.PubMedCrossRefGoogle Scholar
  62. 62.
    Ando M, Hirayama K, Soda K, et al. HLA-DQw3 in Japanese summer-type hypersensitivity pneumonitis induced by Trichosporon cutaneum. Am Rev Respir Dis 1989;140:948–950.PubMedGoogle Scholar
  63. 63.
    Park MH, Kim YW, Yoon HI, et al. Association of HLA class I antigens with diffuse panbronchiolitis. 1999;159:526–529.Google Scholar
  64. 64.
    Keicho N, Tokunaga K, Nakata K, et al. Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis. Am J Respir Crit Care Med 1998;158:846–850.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Armando E. Fraire
    • 1
  1. 1.Department of PathologyUniversity of Massachusetts Medical SchoolWorchesterUSA

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