Complement,granulocytes, and shock lung

Intravascular leukostasis in the pulmonary microvasculature is a cardinal early histologic finding in patients with shock lung. Identical leukostasis is also observed in patients undergoing extracorporeal hemodialysis with cellophane membrane dialyzers, and it has been documented that the accumulation of granulocyte plugs in the lung is mediated by complement activation triggered by dialyzer cellophane. The C5a-desarg so generated causes peripheral blood granulocytes to aggregate, and the aggregates so formed embolize to the lung, where they cause occlusion of the microvasculature and increased capillary leakage, manifested by interstitial and alveolar edema. In vitro studies suggest that this endothelial damage is mediated by hydrogen peroxide from the adherent granulocytes. Most importantly, a close correlation has been found between the presence of C5a-desarg in plasma and the subsequent onset of shock lung in patients after trauma, burns, and sepsis. As exemplified by hemodialysis leukopenia, C5a-desarg-mediated pulmonary leukostasis is a self-limiting process because of selective down-regulation of granulocyte receptors for C5a-desarg—a mechanism that primarily limits the lung damage associated with intravascular complement activation.