Macrophage dysfunction following the phagocytosis of IgG-coated erythrocytes: production of lipid peroxidation products

Abstract

The phagocytosis of erythrocytes may contribute to the increased susceptibility to life-threatening infections in patients with burn injury, sickle cell anemia, and malaria. The phagocytosis of immunoglobulin G-coated erythrocytes (EIgG) is followed by a transient depression of several macrophage functions including phagocytosis, respiratory burst capacity, and killing of bacteria. The present study suggests the possibility that after erythrophagocytosis hemoglobin-derived iron conspires with reactive oxygen products of the macrophage respiratory burst to cause oxidant damage to the phagocyte. Challenge of elicited peritoneal macrophages with EIgG phagocytosis was followed by an increase in lipid peroxidation as assessed by thiobarbituric acid-reactive substances (TBARS). Doses of EIgG associated with increased TBARS also caused a depression of Fc receptor-mediated phagocytosis and phorbol myristate acetate (PMA)-stimulated hydrogen peroxide production. Time course experiments demonstrated that the increase in TBARS coincided with the depression of macrophage function. There was no increase in TBARS following the phagocytosis of IgG-coated erythrocyte ghosts, suggesting that hemoglobin iron is involved in the generation of TBARS. The phagocytosis of erythrocyte ghosts did not depress macrophage function. Since complement receptor-mediated phagocytosis does not stimulate the respiratory burst, the role of the respiratory burst in causing lipid peroxidation was assessed using the phagocytosis of complement-coated erythrocytes. Phagocytic challenge with complement-coated erythrocytes caused neither an increase in TBARS nor a depression of macrophage function. However, there was an increase in TBARS when the respiratory burst was stimulated with PMA following complement receptor-mediated phagocytosis of erythrocytes. These results suggest that hemoglobin iron and phagocyte-generated oxidants collaborate to cause the depression of macrophage function following EIgG phagocytosis.