Our recent studies of skin thermal injury in rats have demonstrated the onset of systemic activation of complement, acquisition of phagocytic cell defects and development of secondary lung injury. The pulmonary complication has been related to intravascular activation of neutrophils, entrapment of leukoaggregates in lungs and the development of pulmonary vascular endothelial injury due to oxygen radical (hydroxyl radical) formation by leukocytes. We now plan to examine both local effects of thermal injury as well as some of the systemic complications (phagocytic cell defects and intravascular hemolysis) arising from localized thermal injury of skin. The proposed studies will focus on mediator systems responsible for the local inflammatory response to thermal injury, the ability of thermally injured parenchymal and mesenchymal cells to activate the complement system, mediators responsible for the acquired defects of phagocytic cells following thermal injury, and the pursuit of preliminary evidence suggesting that intravascular hemolysis associated with thermal injury is probably the combined result of intravascular activation of complement as well as oxygen radical generation by blood neutrophils. The development of flow cytometric techniques to analyze in a quantitative manner unfractionated blood leukocytes from small volumes (0.1 ml) of whole rat blood will greatly facilitate these studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028499-08
Application #
3275770
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1981-01-01
Project End
1990-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Friedl, H P; Till, G O; Trentz, O et al. (1991) Role of oxygen radicals in tourniquet-related ischemia-reperfusion injury of human patients. Klin Wochenschr 69:1109-12
Till, G O; Friedl, H P; Ward, P A (1991) Lung injury and complement activation: role of neutrophils and xanthine oxidase. Free Radic Biol Med 10:379-86
Hatherill, J R; Till, G O; Ward, P A (1991) Mechanisms of oxidant-induced changes in erythrocytes. Agents Actions 32:351-8
Sannomiya, P; Craig, R A; Clewell, D B et al. (1990) Characterization of a class of nonformylated Enterococcus faecalis-derived neutrophil chemotactic peptides: the sex pheromones. Proc Natl Acad Sci U S A 87:66-70
Caty, M G; Schmeling, D J; Friedl, H P et al. (1990) Histamine: a promoter of xanthine oxidase activity in intestinal ischemia/reperfusion. J Pediatr Surg 25:218-22;discussion 222-3
Friedl, H P; Smith, D J; Till, G O et al. (1990) Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity. Am J Pathol 136:491-5
Friedl, H P; Till, G O; Ryan, U S et al. (1989) Mediator-induced activation of xanthine oxidase in endothelial cells. FASEB J 3:2512-8
Friedl, H P; Till, G O; Trentz, O et al. (1989) Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Am J Pathol 135:203-17
Till, G O; Guilds, L S; Mahrougui, M et al. (1989) Role of xanthine oxidase in thermal injury of skin. Am J Pathol 135:195-202

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