Complement-mediated defect in clearance and sequestration of sensitized, autologous erythrocytes in rodent malaria.

We investigated the ability of malaria-infected and normal mice to clear particulate immune complexes consisting of autologous erythrocytes sensitized with either IgG or complement. Normal mice rapidly clear autologous erythrocytes optimally sensitized with IgG and the liver plays a major role in their sequestration. Clearance of optimally sensitized erythrocytes is complement-dependent because cobra venom factor-treated, normal mice failed to clear these cells rapidly, unless they had been pre-treated with fresh mouse serum. In the initial phase of Plasmodium berghei infection, clearance of the optimally sensitized erythrocytes was markedly increased over that observed in normal mice. 2 wk after infection, however, clearance was minimal. This defect was most likely the consequence of the hypocomplementemia observed at this stage of infection since sensitized erythrocytes were removed rapidly from the blood if they had been coated with C3 in vitro before injection into malarial mice.The functional activity of the complement receptors of phagocytic cells was assayed in malarial mice by the injection of autologous erythrocytes coated with C3 and C4 in the absence of antibody. The complement-coated erythrocytes were rapidly removed from the blood, accumulated in the liver, and then gradually returned to the circulation. Similar patterns were observed in normal animals, but the degree of clearance was considerably higher in the malarial mice late in infection. It appears, therefore, that complement receptors remain functional throughout the infection. Erythrocytes suboptimally sensitized with IgG were cleared minimally by normal mice. This clearance was not complement-dependent and was mediated mainly by the spleen. During malaria, clearance of these particles was initially enhanced but later it was abolished.The association of hypocomplementemia with a major splenic defect in clearance late in malaria infection may explain the accumulation of immune complexes in pathological sites observed in this disease.