Effect of intravascular complement activation on granulocyte adhesiveness and distribution

The effects of manipulations that activate complement (C) by the alternate pathway upon the concentration of circulating granulocytes and their adhesiveness were studied in rabbits and humans under several conditions. Whether C is preactivated in vitro and then infused intravenously, activated in vivo by administration of cobra venom factor, or activated during extracorporeal circulation in human hemodialysis, a close correlation between changing granulocyte adhesiveness and granulocyte levels is noted. Shortly after C activation, circulating granulocytes disappear, while their adhesiveness (measured by nylon fiber filtration) increases strikingly. Thereafter, when circulating granulocytes return and actually rebound to above-baseline levels, their adhesiveness declines in parallel. The results suggest that activated C components induce stickiness of granulocytes, which engenders their sequestration. When C-activated plasma is infused intravenously, granulocytes are sequestered selectively in the pulmonary circulation. When C is activated throughout the entire body by the intravenous infusion of cobra venom factor, granulocytes sequester nonselectively. In the former instance, animals develop hypoxemia; in the latter instance, hypoxemia is not observed. Thus granulocytes made hyperadhesive sequester in the first capillary network traversed, and selective organ dysfunction may occur. The results help to explain the recently reported pulmonary leukostasis and dysfunction accompanying hemodialysis.