Regulation of the Lung Inflammatory Response

  • P. A. Ward
  • A. B. Lentsch
Conference paper


Lung inflammatory responses in rat lung induced by deposition of IgG immune complexes are associated with complement activation, influx of neutrophils, activation of pulmonary macrophages and ensuing injury of the lung parenchyma [1]. Injury in this model is associated with extravascular leak of albumin, development of haemorrhage and damage of cellular and matrix constituents. Tissue injury is likely due to the combined effects of oxidants and proteases released from activated lung macrophages and from recruited neutrophils following a complex sequence of cellular and mediator interactions [2]. Essential to an understanding of these inflammatory events is the relationship between lung macrophage production of cytokines [such as tumor necrosis factor-alpha (TNFα) and interleukin-1 (IL-1)] and the response of the lung vasculature, the result of which is upregulation of endothelial adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin. We have found that these lung inflammatory reactions are carefully self-regulated. That is to say, the intensity of the inflammatory response builds up to a crescendo, peaking between 3–4 hours, then rapidly diminishes, as reflected by a reduction in vascular permeability, a cessation in haemorrhage and no further accumulation of neutrophils [3]. In some manner, then, these inflammatory responses are under regulatory control that ensures the potentially destructive inflammatory response will be contained.


NFKB Activation Endothelial Adhesion Molecule Lung Macrophage Vascular Adhesion Molecule Complement Activation Product 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Johnson KJ, Ward PA (1974) Acute immunologic pulmonary alveolitis. J Clin Invest 54: 349–357PubMedCrossRefGoogle Scholar
  2. 2.
    Lukacs NW, Ward PA (1996) Inflammatory mediators, cytokines, and adhesion molecules in pulmonary inflammation and injury. In: Dixon FJ (ed) Advances in immunology, vol. 62. Academic Press, Orlando, pp 257–304Google Scholar
  3. 3.
    Lentsch AB, Czermak BJ, Bless NM, Ward PA (1998) NF-kB activation during IgG immune complex-induced lung injury. Am J Pathol 152:1327–1336PubMedGoogle Scholar
  4. 4.
    Hugli TE (1986) Biochemistry and biology of anaphylatoxins. Complement 3:111–127PubMedGoogle Scholar
  5. 5.
    Mulligan MS, Vaporciyan AA, Miyasaka M et al (1993) Tumor necrosis factor a regulates in vivo intrapulmonary expression of ICAM-1. Am J Pathol 142:1739–1749PubMedGoogle Scholar
  6. 6.
    Warren JS (1991) Intrapulmonary interleukin 1 mediates acute immune complex alveolitis in the rat. Biochem Biophys Res Commun 175:604–610PubMedCrossRefGoogle Scholar
  7. 7.
    Mulligan MS, Varani J, Dame MK et al (1991) Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J Clin Invest 88:1396–1406PubMedCrossRefGoogle Scholar
  8. 8.
    Kilgore KS, Shen JP, Miller BF et al (1995) Enhancement by the complement membrane attack complex of tumor necrosis factor-α induced endothelial cell expression of E-selectin and ICAM-1. J Immunol 155:1434–1441PubMedGoogle Scholar
  9. 9.
    Hattori R, Hamilton KK, Fugate RD et al (1998) Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem 264:7768–7771Google Scholar
  10. 10.
    Foreman KE, Vaporciyan AA, Bonish BK et al (1994) C5a-induced expression of P-selectin in endothelial cells. J Clin Invest 94:1147–1155PubMedCrossRefGoogle Scholar
  11. 11.
    Kilgore KS, Ward PA, Warren JS ( 1998) Neutrophil adhesion to human endothelial cells is induced by the membrane attack complex: The roles of P-selectin and platelet activating factor. Inflammation (in press)Google Scholar
  12. 12.
    Mulligan MS, Ward PA (1992) Immune complex-induced lung and dermal vascular injury: Differing requirements for TNFα and IL-1. J Immunol 149:331–339PubMedGoogle Scholar
  13. 13.
    Liou HC, Baltimore D (1993) Regulation of the NF-kappa B/rel transcription factor and I kappa B inhibitor system. Curr Opin Cell Biol 5:477–487PubMedCrossRefGoogle Scholar
  14. 14.
    Baldwin AS (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683PubMedCrossRefGoogle Scholar
  15. 15.
    Kilgore KS, Schmid E, Shanley TP et al (1997) Sublytic concentrations of the membrane attack complex (MAC) of complement induce endothelial interleukin 8 (IL-8) and monocyte protein 1 (MCP-1) through nuclear factor kappa-B (NF-kB) activation. Am J Pathol 150(6): 2019–2031PubMedGoogle Scholar
  16. 16.
    Zimmerman GA, Prescott SM, Mclntyre TM (1998) Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol Today 13:93–99CrossRefGoogle Scholar
  17. 17.
    Mulligan MS, Jones ML, Vaporciyan AA et al (1993) Protective effects of IL-4 and IL-10 against immune complex-induced lung injury. J Immunol 151:5666–5674PubMedGoogle Scholar
  18. 18.
    Mulligan MS, Warner RL, Foreback JL et al (1997) Protective effects of IL-4, IL-10, IL-12, and IL-13 in IgG immune complex-induced lung injury; role of endogenous IL-12. J Immunol 159:3483–3489PubMedGoogle Scholar
  19. 19.
    Shanley TP, Foreback JL, Remick DG et al (1997) Regulatory effects of IL-6 in IgG immune complex-induced lung injury. Am J Pathol 151(1): 193–203PubMedGoogle Scholar
  20. 20.
    Shanley TP, Schmal H, Friedl HP et al (1995) Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury. J Immunol 154:3454–3460PubMedGoogle Scholar
  21. 21.
    Schimmer RC, Schrier DJ, Flory CM et al (1998) Streptococcal cell wall-induced arthritis: requirements for IL-4, IL-10, Interferon-y and MCP-1. J Immunol 160:1466–1471PubMedGoogle Scholar
  22. 22.
    Lentsch AB, Czermak BJ, Bless et al (1998) NF-kB activation during IgG immune complex-induced lung injury: requirements for TNFα and IL-1ß but not complement. Am J Pathol 152:1327–1336PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 1999

Authors and Affiliations

  • P. A. Ward
  • A. B. Lentsch

There are no affiliations available

Personalised recommendations