Activation of complement by hydroxyl radical in thermal injury.
Complement activation resulting from local burn injury of skin and other soft tissues can be linked to systemic complications, such as intravascular hemolysis, neutrophil activation, and acute lung injury. This study was designed to clarify the relationship between cutaneous thermal injury, oxygen radical formation, and complement activation in vivo. A model for "selective" venous sampling from the area of a partial-thickness cutaneous burn over 25% to 30% of the total body surface in the rat was developed. Interventions involving oxygen radical scavengers, antioxidant enzymes, xanthine oxidase inhibitors, an iron chelator, complement depletion, and neutrophil depletion were used to probe the nature of the oxygen products involved in complement activation. Plasma from the area of burn was examined for total hemolytic complement activity, content of C5a-related chemotactic peptide, and relationship of oxygen products to appearance of this peptide. Xanthine oxidase inhibitors, hydroxyl radical scavengers, and complement depletion diminished the generation of C5a activity at the burn site, whereas neutrophil depletion was without effect. These data suggest that C5a activity may be related to oxygen products from xanthine oxidase. The catalase sensitivity and iron dependency of C5a generation suggest that hydroxyl radical may be related to complement activation and C5a appearance. This is the first report to directly link oxygen radical generation and complement activation in vivo.
Oldham
K T
KT
Department of Surgery, University of Michigan Medical School, Ann Arbor.
Guice
K S
KS
Till
G O
GO
Ward
P A
PA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002056:Burns / Q000276:immunology* / Q000378:metabolism; D002630:Chemotactic Factors / Q000032:analysis*; D003167:Complement Activation; D003182:Complement C5 / Q000032:analysis*; D015936:Complement C5a; D003165:Complement System Proteins / Q000032:analysis; D008212:Lymphocyte Depletion; D008297:Male; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000975:Antioxidants; D002630:Chemotactic Factors; D003182:Complement C5; D013481:Superoxides; D015936:Complement C5a; D003165:Complement System Proteins; D014969:Xanthine Oxidase