Complement component C5 deficiency reduces edema formation in murine ligation-induced acute pancreatitis.
The complement cascade is activated in humans and animals with acute pancreatitis. Activation of complement component C5 liberates C5a, C5a-desarg, and terminal complement complexes (TCCs) that increase capillary permeability, edema, and leukocyte chemotaxis at injured sites. Complement activation plays a major role in pathogenesis of capillary leak and edema formation in severe acute pancreatitis; however, the contribution of C5 (C5a/C5a-desarg, TCCs) has not been defined. Using He gene mutant mice lacking circulating C5, the role of C5 in ligation-induced acute pancreatitis was evaluated. We performed the following experiments: C5-sufficient (Hc1/Hc1) and C5-deficient (Hc0/Hc0) mice had bile and pancreatic ducts ligated. Sham-operated mice had ducts dissected but not ligated. Mice were killed at 4, 8, and 24 hr after bilepancreatic duct ligation. Serologic and morphologic evidences of acute pancreatitis were evaluated. Pancreatic edema was assessed using analysis of pancreatic water content, histologic edema score, and determination of wet weight ratio. After 4, 8, and 24 hr of bile-pancreatic duct ligation, hyperamylasemia and histologic changes of acute pancreatitis were observed in both C5-deficient and C5-sufficient mice. Edema developed in all mice with acute pancreatitis. However, when compared to C5-sufficient mice, mice deficient in C5 developed significantly less pancreatic edema at both 8 and 24 hr of bile-pancreatic duct ligation. This difference was not observed 4 hr after induction of acute pancreatitis. We conclude that C5 contributes to edema formation in murine ligation-induced acute pancreatitis. The presence of an early C5-independent phase, in conjunction with the observation of significant edema in mice deficient in C5, suggests there are other mediators of edema formation in this acute pancreatitis model.
Merriam
L T
LT
Department of Surgery, Northwestern University Medical School, Chicago, Illinois, USA.
Webster
C
C
Joehl
R J
RJ
D000681:Amylases / Q000097:blood; D000818:Animals; D003182:Complement C5 / Q000172:deficiency / Q000502:physiology*; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology* / Q000473:pathology; D008026:Ligation; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000150:complications* / Q000209:etiology / Q000473:pathology
D003182:Complement C5; D000681:Amylases