Complement-mediated granulocyte activation and down-regulation during hemodialysis

Intravascular leukostasis is observed in the lungs of patients undergoing hemodialysis with cellophane membrane dialyzers, a phenomenon we have shown to result from complement activation triggered by contact with the cellophane. The C5a-desarg so generated causes peripheral blood granulocytes to aggregate and to become more adhesive. The aggregated granulocytes embolize to the lung where they cause occlusion of the microvasculature and increased capillary leakage manifested by interstitial and alveolar edema. In vitro studies suggested that endothelial damage is mediated by toxic oxidant species from the adherent stimulated granulocytes. More recently we have shown that this C5a-desarg-mediated pulmonary leukostasis is a self-limiting process because of selective down-regulation (deactivation) of granulocyte receptors for C5a-desarg. This mechanism limits the lung damage associated with intravascular complement activation during hemodialysis, but may also be important in promoting the propensity for infection observed in these patients.