Regulatory Role of Alveolar Macrophages and Cytokines in Pulmonary Host Defense

  • M. J. Schultz
  • S. Knapp
  • T. van der Poll

Abstract

The lungs are repeatedly exposed to respiratory pathogens, either by inhalation or (micro-) aspiration of microorganisms that colonize the oropharynx. Infectious agents that have passed the structural defenses and have entered the terminal airways may cause pneumonia, one of the most common infectious diseases. Both the growing number of immunocompromised patients susceptible to pneumonia, and the widespread use of antibiotics that has led to a rise in antibiotic resistance among microorganisms, have made the treatment of pneumonia more difficult. Hence, there is a need for novel therapeutic approaches for pneumonia. Immunotherapy, aimed at modulating the immune response, is one such approach. Immunotherapy may serve as an important adjuvant to antibiotic therapy in the treatment of infectious diseases. However, before such immunotherapies can become serious tools in the treatment of severe pneumonia, increased knowledge of the immune host defense is needed.

Keywords

Host Defense Alveolar Macrophage Respiratory Pathogen Pneumococcal Pneumonia Bacterial Clearance 
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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References

  1. 1.
    Hashimoto S, Pittet JF, Hong K, et al (1996) Depletion of alveolar macrophages decreases neutrophil chemotaxis to Pseudomonas airspace infections. Am J Physiol 270: L819 - L828PubMedGoogle Scholar
  2. 2.
    Harmsen AG (1988) Role of alveolar macrophages in lipopolysaccharide-induced neutro-phil accumulation. Infect Immun 56: 1858–1863PubMedGoogle Scholar
  3. 3.
    Ren Y, Savill J (1995) Proinflammatory cytokines potentiate thrombospondin-mediated phagocytosis of neutrophils undergoing apoptosis. J Immunol 154: 2366–2374PubMedGoogle Scholar
  4. 4.
    Cox G (1996) IL-10 enhances resolution of pulmonary inflammation in vivo by promoting apoptosis of neutrophils. Am J Physiol 271: L566 - L571PubMedGoogle Scholar
  5. 5.
    Knapp S, Leemans JC, Maris NA, et al (2001) Alveolar macrophages protect mice against lethality during Streptococcus pneumoniae pneumonia by attenuating lung inflammation. 41st ICACC Abstract Book. ASM press, Herndon. (Abst, in press)Google Scholar
  6. 6.
    Hickman-Davis JM, Michalek SM, Gibbs-Erwin J, Lindsey JR (1997) Depletion of alveolar macrophages exacerbates respiratory mycoplasmosis in mycoplasma-resistant C57BL mice but not mycoplasma-susceptible C3H mice. Infect Immun 65: 2278–2282PubMedGoogle Scholar
  7. 7.
    Broug-Holub E, Kraal G (1997) In vivo study on the immunomodulating effects of 0M-85 BV on survival, inflammatory cell recruitment and bacterial clearance in Klebsiella pneumonia. Int J Immunopharmacol 19: 559–564PubMedCrossRefGoogle Scholar
  8. 8.
    Cheung DO, Halsey K, Speert DP (2000) Role of pulmonary alveolar macrophages in defense of the lung against Pseudomonas aeruginosa. Infect Immun 68: 4585–4592PubMedCrossRefGoogle Scholar
  9. 9.
    Kooguchi K, Hashimoto S, Kobayashi A, et al (1998) Role of alveolar macrophages in initiation and regulation of inflammation in Pseudomonas aeruginosa pneumonia. Infect Immun 66: 3164–3169PubMedGoogle Scholar
  10. 10.
    Haslett C (1999) Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med 160: 55 - S11CrossRefGoogle Scholar
  11. 11.
    Cox G, Crossley J, Xing Z (1995) Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. Am J Respir Cell Mol Biol 12: 232–237PubMedCrossRefGoogle Scholar
  12. 12.
    Hussain N, Wu F, Zhu L, Thrall RS, Kresch MJ (1998) Neutrophil apoptosis during the development and resolution of oleic acid-induced acute lung injury in the rat. Am J Respir Cell Mol Biol 19: 867–874PubMedCrossRefGoogle Scholar
  13. 13.
    Fadok VA, Savill JS, Haslett C, et al (1992) Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol 149: 4029–4035PubMedGoogle Scholar
  14. 14.
    Savill J, Hogg N, Ren Y, Haslett C (1992) Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest 90: 1513–1522PubMedCrossRefGoogle Scholar
  15. 15.
    Fadok VA, Bratton DL, Rose DM, et al (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405: 85–90PubMedCrossRefGoogle Scholar
  16. 16.
    Fadok VA, Bratton DL, Guthrie L, Henson PM (2001) Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases. J Immunol 166: 6847–6854PubMedGoogle Scholar
  17. 17.
    Dehoux MS, Boutten A, Ostinelli J, et al (1994) Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 150: 710–716PubMedCrossRefGoogle Scholar
  18. 18.
    van der Poll T, Keogh CV, Buurman WA, Lowry SF (1997) Passive immunization against tumor necrosis factor-alpha impairs host defense during pneumococcal pneumonia in mice. Am J Respir Crit Care Med 155: 603–608PubMedCrossRefGoogle Scholar
  19. 19.
    Takashima K, Tateda K, Matsumoto T, et al (1997) Role of tumor necrosis factor alpha in pathogenesis of pneumococcal pneumonia in mice. Infect Immun 65: 257–260PubMedGoogle Scholar
  20. 20.
    Laichalk LL, Kunkel SL, Strieter RM, et al (1996) Tumor necrosis factor mediates lung antibacterial host defense in murine Klebsiella pneumonia. Infect Immun 64: 5211–5218PubMedGoogle Scholar
  21. 21.
    Gosselin D, DeSanctis J, Boule M, et al (1995) Role of tumor necrosis factor alpha in innate resistance to mouse pulmonary infection with Pseudomonas aeruginosa. Infect Immun 63: 3272–3278PubMedGoogle Scholar
  22. 22.
    Brieland JK, Remick DG, Freeman PT, et al (1995) In vivo regulation of replicative Legionella pneumophila lung infection by endogenous tumor necrosis factor alpha and nitric oxide. Infect Immun 63: 3253–3258PubMedGoogle Scholar
  23. 23.
    Beutler B (1995) TNF, immunity and inflammatory disease: lessons of the past decade. J Investig Med 43: 227–235PubMedGoogle Scholar
  24. 24.
    Le J, Vilcek J (1987) Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 56: 234–248PubMedGoogle Scholar
  25. 25.
    Tan AM, Ferrante A, Goh DH, Roberton DM, Cripps AW (1995) Activation of the neutro-phi] bactericidal activity for nontypable Haemophilus influenzae by tumor necrosis factor and lymphotoxin. Pediatr Res 37: 155–159PubMedCrossRefGoogle Scholar
  26. 26.
    Oswald IP, Wynn TA, Sher A, James SL (1992) Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation. Proc Natl Acad Sci USA 89: 8676–8680PubMedCrossRefGoogle Scholar
  27. 27.
    Huffnagle GB, Toews GB, Burdick MD, et al (1996) Afferent phase production of TNF-alpha is required for the development of protective T cell immunity to Cryptococcus neoformans. J Immunol 157: 4529–4536PubMedGoogle Scholar
  28. 28.
    Amura CR, Fontan PA, Sanjuan N, et al (1995) Tumor necrosis factor alpha plus interleukin 1 beta treatment protects granulocytopenic mice from Pseudomonas aeruginosa lung infection: role of an unusual inflammatory response. APMIS 103: 447–459PubMedCrossRefGoogle Scholar
  29. 29.
    Amura CR, Fontan PA, Sanjuan N, Sordelli DO (1994) The effect of treatment with interleukin-1 and tumor necrosis factor on Pseudomonas aeruginosa lung infection in a granulocytopenic mouse model. Clin Immunol Immunopathol 73: 261–266PubMedCrossRefGoogle Scholar
  30. 30.
    Standiford TJ, Wilkowski JM, Sisson TH, et al (1999) Intrapulmonary tumor necrosis factor gene therapy increases bacterial clearance and survival in murine gram-negative pneumonia. Hum Gene Ther 10: 899–909PubMedCrossRefGoogle Scholar
  31. 31.
    Rijneveld AW, Florquin S, Branger J, et al (2001) Tumor necrosis factor-alpha compensates for the impaired host defense of IL-1 type I receptor deficient mice during pneumococcal pneumonia. J Immunol 167: 5240–5246PubMedGoogle Scholar
  32. 32.
    Boutten A, Dehoux MS, Seta N, et al (1996) Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumonia. Am J Respir Grit Care Med 153: 336–342CrossRefGoogle Scholar
  33. 33.
    Rodriguez JL, Miller CG, DeForge LE, et al (1992) Local production of interleukin-8 is associated with nosocomial pneumonia. J Trauma 33: 74–81PubMedCrossRefGoogle Scholar
  34. 34.
    Broaddus VC, Hebert CA, Vitangcol RV, et al (1992) Interleukin-8 is a major neutrophil chemotactic factor in pleural liquid of patients with empyema. Am Rev Respir Dis 146: 825–830PubMedCrossRefGoogle Scholar
  35. 35.
    Schultz MJ, Wijnholds J, Peppelenbosch MP, et al (2001) Mice lacking the multidrug resistance protein 1 are resistant to Streptococcus pneumoniae-Induced pneumonia. J Immunol 166: 4059–4064PubMedGoogle Scholar
  36. 36.
    Greenberger MJ, Strieter RM, Kunkel SL, et al (1996) Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia. J Infect Dis 173: 159–165PubMedCrossRefGoogle Scholar
  37. 37.
    Tsai WC, Strieter RM, Wilkowski JM, et al (1998) Lung-specific transgenic expression of KC enhances resistance to Klebsiella pneumoniae in mice. J Immunol 161: 2435–2440PubMedGoogle Scholar
  38. 38.
    Kooguchi K, Hashimoto S, Kobayashi A, et al (1998) Role of alveolar macrophages in initiation and regulation of inflammation in Pseudomonas aeruginosa pneumonia. Infect Immun 66: 3164–3169PubMedGoogle Scholar
  39. 39.
    Schultz MJ, Rijneveld AW, Speelman P, Deventer SJ, van der Poll T (2001) Endogenous interferon-gamma impairs bacterial clearance from lungs during Pseudomonas aeruginosa pneumonia. Eur Cytokine Netw 12: 39–44PubMedGoogle Scholar
  40. 40.
    Moore TA, Newstead MW, Strieter RM, et al (2000) Bacterial clearance and survival are dependent on CXC chemokine receptor-2 ligands in a murine model of pulmonary Nocardia asteroides infection. J Immunol 164: 908–915PubMedGoogle Scholar
  41. 41.
    Tsai WC, Strieter RM, Mehrad B, et al (2000) CXC chemokine receptor CXCR2 is essential for protective innate host response in murine Pseudomonas aeruginosa pneumonia. Infect Immun 68: 4289–4296PubMedCrossRefGoogle Scholar
  42. 42.
    Rubins JB, Pomeroy C (1997) Role of gamma interferon in the pathogenesis of bacteremic pneumococcal pneumonia. Infect Immun 65: 2975–2977PubMedGoogle Scholar
  43. 43.
    Rijneveld AW, Lauw FN, Schultz MJ, et al (2002) The role of interferon-gamma in murine pneumococcal pneumonia. J Infect Dis 185: 91–97PubMedCrossRefGoogle Scholar
  44. 44.
    Greenberger MJ, Kunkel SL, Strieter RM, et al (1996) IL-12 gene therapy protects mice in lethal Klebsiella pneumonia. J Immunol 157: 3006–3012PubMedGoogle Scholar
  45. 45.
    Tsai WC, Strieter RM, Zisman DA, et al (1997) Nitric oxide is required for effective innate immunity against Klebsiella pneumoniae. Infect Immun 65: 1870–1875PubMedGoogle Scholar
  46. 46.
    Zisman DA, Strieter RM, Kunkel SL, et al (1998) Ethanol feeding impairs innate immunity and alters the expression of Thl-and Th2-phenotype cytokines in murine Klebsiella pneumonia. Alcohol Clin Exp Res 22: 621–627PubMedCrossRefGoogle Scholar
  47. 47.
    Murray HW (1988) Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med 108: 595–608PubMedCrossRefGoogle Scholar
  48. 48.
    Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-gamma. Annu Rev Immunol 15: 749–795PubMedCrossRefGoogle Scholar
  49. 49.
    Lauw F, Florquin S, Akira S, et al (2001) IL-18 has a protective role in the early antimicrobial host response to pneumococcal pneumonia. J Immunol 69: 5949–5952Google Scholar
  50. 50.
    Kolls JK, Lei D, Nelson S, et al (1995) Adenovirus-mediated blockade of tumor necrosis factor in mice protects against endotoxic shock yet impairs pulmonary host defense. J Infect Dis 171: 570–575PubMedCrossRefGoogle Scholar
  51. 51.
    Kolls JK, Lei D, Nelson S, Summer WR, Shellito JE (1997) Pulmonary cytokine gene therapy. Adenoviral-mediated murine interferon gene transfer compartmentally activates alveolar macrophages and enhances bacterial clearance. Chest 111 (suppl 6): 104SPubMedCrossRefGoogle Scholar
  52. 52.
    Kolls JK, Lei D, Stoltz D, et al (1998) Adenoviral-mediated interferon-gamma gene therapy augments pulmonary host defense of ethanol-treated rats. Alcohol Clin Exp Res 22: 157–162PubMedCrossRefGoogle Scholar
  53. 53.
    Ye P, Rodriguez FH, Kanaly S, et al (2001) Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194: 519–527PubMedCrossRefGoogle Scholar
  54. 54.
    Laichalk LL, Danforth JM, Standiford TJ (1996) Interleukin-10 inhibits neutrophil phagocytic and bactericidal activity. FEMS Immunol Med Microbiol 15: 181–187PubMedCrossRefGoogle Scholar
  55. 55.
    Ralph P, Nakoinz I, Sampson-Johannes A, et al (1992) IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol 148: 808–814PubMedGoogle Scholar
  56. 56.
    van der Poll T, Marchant A, Keogh CV, Goldman M, Lowry SF (1996) Interleukin-10 impairs host defense in murine pneumococcal pneumonia. J Infect Dis 174: 994–1000PubMedCrossRefGoogle Scholar
  57. 57.
    Greenberger MJ, Strieter RM, Kunkel SL, et al (1995) Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia. J Immunol 155: 722–729PubMedGoogle Scholar
  58. 58.
    van der Poll T, Keogh CV, Guirao X, et al (1997) Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia. J Infect Dis 176: 439–444PubMedCrossRefGoogle Scholar
  59. 59.
    Skerrett SJ, Martin TR, Chi EY, et al (1999) Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin or Pseudomonas aeruginosa. Am J Physiol 276: L715 - L727PubMedGoogle Scholar
  60. 60.
    Schultz MJ, Speelman P, van Deventer SJH, van der Poll T (1999) The role of IL-1 in inflammation during Pseudomonas aeruginosa pneumonia in mice. 39th ICAAC Abstract Book. ASM Press, Herndon, pp 383 (Abst)Google Scholar
  61. 61.
    Sawa T, Corry DB, Gropper MA, et al (1997) IL-10 improves lung injury and survival in Pseudomonas aeruginosa pneumonia. J Immunol 159: 2858–2866PubMedGoogle Scholar
  62. 62.
    Steinhauser ML, Hogaboam CM, Kunkel SL, et al (1999) IL-10 is a major mediator of sepsis-induced impairment in lung antibacterial host defense. J Immunol 162: 392–399PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • M. J. Schultz
  • S. Knapp
  • T. van der Poll

There are no affiliations available

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