Inflammation

, Volume 22, Issue 6, pp 619–629 | Cite as

Mediators of Microvascular Injury in Dermal Burn Wounds

  • Z. B. Ravage
  • H. F. Gomez
  • B. J. Czermak
  • S. A. Watkins
  • G. O. Till
Article

Abstract

In previous studies we have demonstrated that second-degree thermal injury of skin in rats leads to secondary effects, such as systemic complement activation, C5a-mediated activation of blood neutrophils, their adhesion-molecule-guided accumulation in lung capillaries and the development of acute pulmonary injury, largely caused by neutrophil-derived toxic oxygen metabolites. In the dermal burn wound, however, pathophysiologic events are less well understood. The injury is fully developed at four hours post-burn. To further elucidate the pathogenesis of the “late phase” dermal vascular damage, rats were depleted of neutrophils or complement by pretreatment with rabbit antibody against rat neutrophils or with cobra venom factor, respectively. In other experiments, rats were treated with blocking antibodies to IL-6, IL-1, and TNFα immediately following thermal burning or were pretreated with hydroxyl radical scavengers (dimethyl sulfoxide, dimethyl thiourea). Extravasation of 125I-labeled bovine serum albumin into the burned skin was studied, as well as, skin myeloperoxidase levels. The studies revealed that, like in secondary lung injury, neutrophils and toxic oxygen metabolites, are required for full development of microvascular injury. In contrast, however, development of dermal vascular damage in thermally injured rats was not affected by complement depletion. Our data suggest that the development of microvascular injury in the dermal burn wound is complement-independent, involves the pro-inflammatory cytokines IL-1, TNFα and IL-6, and may result from reactive oxygen metabolites generated by neutrophils accumulating in the burn wound.

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REFERENCES

  1. 1.
    Mann, R. and D. Heimbach. 1996. Prognosis and treatment of burns. West. J. Med. 165:215–220.PubMedGoogle Scholar
  2. 2.
    Till, G. O., C. Beauchamp, D. Menpace, W. Tourtellotte Jr., R. Kunkel, K. J. Johnson, and P. A. Ward. 1983. Oxygen radical dependent lung damage following thermal injury of rat skin. J. Trauma. 23:269–273.PubMedGoogle Scholar
  3. 3.
    Mulligan, M. S., G. O. Till, C. W. Smith, D. C. Anderson, M. Miyasaka, T. Tamatani, R. F. Todd, III, T. B. Issekutz, and P. A. Ward. 1994. Role of leukocyte adhesion molecules in lung and dermal vascular injury after thermal trauma of skin. Am. J. Pathol. 144:1008–1015.PubMedGoogle Scholar
  4. 4.
    Demling, R. H. 1985. Burns. N. Engl. J. Med. 313: 1389–1398.PubMedGoogle Scholar
  5. 5.
    Freidl, H. P., G. O. Till, O. Trentz, and P. A. Ward. 1989. Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Am. J. Pathol. 135:203–217.PubMedGoogle Scholar
  6. 6.
    Till, G. O., L. S. Guilds, M. Mahrougui, H. P. Freidl, O. Trentz, and P. A. Ward. 1989. Role of xanthine oxidase in thermal injury of skin. Am. J. Pathol. 135:195–202.PubMedGoogle Scholar
  7. 7.
    Till, G. O., J. R. Hatherill, W. W. Tourtellotte, M. J. Lutz, and P. A. Ward. 1985. Lipid peroxidation and acute lung injury after thermal trauma to skin: Evidence of a role for hydroxyl radical. Am. J. Pathol. 135:195–202.Google Scholar
  8. 8.
    Ballow, M. and C. G. Cochrane. 1969. Two anti-complementary factors in cobra venom. Hemolysis of guinea pig erythrocytes by one of them. J. Immunol. 103:944–952.PubMedGoogle Scholar
  9. 9.
    Mulligan, M. S., E. Schmid, B. Beck-Schimmer, G. O. Till, H. P. Friedl, R. B. Brauer, T. E. Hugli, M. Miyasaka, R. L. Warner, K. J. Johnson, and P. A. Ward. 1996. Requirement and role of C5a in Acute Lung Inflammatory Injury in Rats. J. Clin. Invest. 98:503–512.PubMedGoogle Scholar
  10. 10.
    Prober, J. S. and R. S. Cotran. 1990. The role of endothelial cells in inflammation. Transplantation. 50:537–544.PubMedGoogle Scholar
  11. 11.
    Bevilacqua, M. P., J. S. Prober, D. L. Mendrick, R. S. Cotran, and M. A. Gimbrone, JR. 1987. Identification of an inducible endothelial-leukocyte adhesion molecule. Proc. Natl. Acad. Sci. U.S.A. 84:9238–9242.PubMedGoogle Scholar
  12. 12.
    Bevilacqua, M. P., S. Stengelin, M. A. Gimbrone, and B. Seed. 1989. Endothelial leukocyte adhesion molecule 1: An inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243:1160–1165.PubMedGoogle Scholar
  13. 13.
    Osborn, L., C. Hession, R. Tizard, C. Vassallo, S. Luhowskyj, G. Chi-Rosso, and R. Lobb. 1989. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 60:577–584.Google Scholar
  14. 14.
    Dustin, M. A. and T. A. Springer. 1988. Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultures endothelial cells. J. Cell Biol. 107:321–331.CrossRefPubMedGoogle Scholar
  15. 15.
    Content, J., L. De Wit, P. Poupart, G. Opdenakker, J. Van Damme, and A. Billiau. 1985. Induction of a 26-kDa-protein mRNA in human cells treated with and interleukin-1-related, leukocyte-derived factor. Eur. J. Biochem. 152:253–257.PubMedGoogle Scholar
  16. 16.
    Kasid, A., E. P. Director, and S. A. Rosenberg. 1989. Regulation of interleukin-6 (IL-6) by IL-2 and TNF-α in human peripheral blood mononuclear cells. Ann. N.Y. Acad. Sci. 557:564–566.Google Scholar
  17. 17.
    Maruo, N., I. Morita, M. Shirao, and S. Murota. 1992. IL-6 increases endothelial permeability in vitro. Endocrinology 131:710–714.CrossRefPubMedGoogle Scholar
  18. 18.
    Biffl, W. L., E. E. Moore, F. A. Moore, V. S. Carl, F. J. Kim, and R. J. Franciose. 1994. Interleukin-6 potentiates neutrophil priming with platelet-activating factor. Arch. Surg. 129:1131–1136.PubMedGoogle Scholar
  19. 19.
    Biffl, W. L., E. E. Moore, F. A. Moore, and C. C. Barnett. 1996. Interleukin-6 delays neutrophil apoptosis via a mechanism involving platelet-activating factor. J. Trauma 40:575–579.PubMedGoogle Scholar
  20. 20.
    Mullen, P. G., A. C. J. Windsor, C. J. Walsh, A. A. Fowler, III, and H. J. Sugarman. 1995. Tumor necrosis factor-α and IL-6 selectively regulate neutrophil function in vitro. J. Surg. Res. 58:124–130.CrossRefPubMedGoogle Scholar
  21. 21.
    Youker, K., C. W. Smith, D. C. Anderson, D. Miller, L. H. Michael, R. D. Rossen, and M. L. Entman. 1992. Neutrophil adherence to isolated adult cardiac myocytes: Induction by cardiac lymph collected during ischemia and reperfusion. J. Clin. Invest. 89:602–609.PubMedGoogle Scholar
  22. 22.
    Yasojima, K., K. S. Kilgore, R. A. Washington, B. R. Lucchesi, and P. L. McGeer. 1998. Complement gene expression by rabbit heart: Upregulation by ischemia and reperfusion. Circ. Res. 82:1224–1230.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Z. B. Ravage
    • 1
  • H. F. Gomez
    • 1
  • B. J. Czermak
    • 1
  • S. A. Watkins
    • 1
  • G. O. Till
    • 1
  1. 1.University of Michigan Medical SchoolAnn Arbor

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