Acute thermal injury results in activation of the complement system and the following outcomes: recruitment and activation of neutrophil; their subsequent generation of toxic oxygen products; and resulting intravascular hemolysis and injury of the pulmonary microvasculature. While the basis for complement activation is not know, Vogt et al. (1) have recently shown in vitro that H202 will trigger the generation in plasma of C5a. The proposed studies will deal with several relevant topics. We will study both in vitro and in vivo the relationship between oxygen radical generation and activation of the complement system resulting in the formation of C5a. The in vitro studies will involve the use of activated neutrophils and enzyme-substrate mixtures. The in vivo studies will focus on the relationship between the appearance of C5a in plasma and the nature of the oxygen relationship between the appearance of C5a in plasma and the nature of the oxygen product involved as well as is origin (NADPH oxidase versus xanthine oxidase). We will assess the role of xanthine oxidase further using experiments in vitro and in vivo to determine if thermal injury to skin or cultured rat pulmonary microvascular endothelial cells causes the conversion of xanthine dehydrogenase to xanthine oxidase. We will also assess the possibility that following thermal injury to the skin a state of ischemia-radicals and complement activation. Experiments will be employed using surgical manipulations to induce a state of ischemia in order to determine if this results in complement activation. It is anticipated that these studies should provide evidence for the relationship between acute thermal injury, oxygen radical information, and complement activation.
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| Turnage, R H; Guice, K S; Oldham, K T (1994) Pulmonary microvascular injury following intestinal reperfusion. New Horiz 2:463-75 |
| Magee, J C; Platt, J L; Oldham, K T et al. (1994) Oxidant stress increases susceptibility of porcine endothelial cells to injury by xenoreactive antibody and complement. Transplant Proc 26:1170 |
| Guice, K S; Oldham, K T; Remick, D G et al. (1991) Anti-tumor necrosis factor antibody augments edema formation in caerulein-induced acute pancreatitis. J Surg Res 51:495-9 |
| Turnage, R H; Bagnasco, J; Berger, J et al. (1991) Hepatocellular oxidant stress following intestinal ischemia-reperfusion injury. J Surg Res 51:467-71 |
