BIOLOGICAL ACTIVITY OF COMPLEMENT IN VIVO : ROLE OF C5 IN THE ACCUMULATION OF POLYMORPHONUCLEAR LEUKOCYTES IN INFLAMMATORY EXUDATES

The importance of C5 in the generation of complement (C)-dependent chemotactic activity in vitro is well recognized. However, the actual role C5 may play in the accumulation of polymorphonuclear leukocytes (PMN) at inflammatory sites in vivo has not been established. Injection of glycogen or endotoxin into the peritoneal cavities of guinea pigs resulted, shortly thereafter, in the local accumulation of PMN. Preceding the influx of leukocytes, the peritoneal fluid became chemotactic for rabbit PMN in vitro. The majority of this activity could be attributed to a cleavage product of C5 (C5a). Similarly, injection of endotoxin into the peritoneal cavity of C5-normal mice resulted in the generation of a chemotactic factor for mouse PMN which was followed by the accumulation of PMN in the peritoneal fluid. In contrast, injection of endotoxin into the peritoneal cavity of C5-deficient mice resulted in the generation of virtually no detectable chemotactic activity and a markedly depressed accumulation of PMN during the first 24 hr after injection. The data suggest that C5 plays an important role in the early phases of PMN accumulation in response to inflammatory stimuli. The rapid accumulation of PMN in response to an inflammatory stimulus such as bacterial endotoxin would be expected to be a major factor in host defense against proliferation and dissemination of infectious agents.