MACROPHAGE DYSFUNCTION FOLLOWING THE PHAGOCYTOSIS OF IGG-COATED ERYTHROCYTES - PRODUCTION OF LIPID-PEROXIDATION PRODUCTS

The phagocytosis of erythrocytes may contribute to the increased susce ptibility 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 s everal macrophage functions including phagocytosis, respiratory burst capacity, and killing of bacteria, The present study suggests the poss ibility that after erythrophagocytosis hemoglobin-derived iron conspir es with reactive oxygen products of the macrophage respiratory burst t o cause oxidant damage to the phagocyte, Challenge of elicited periton eal macrophages with EIgG phagocytosis was followed by an increase in Lipid peroxidation as assessed by thiobarbituric acid-reactive substan ces (TEARS), Doses of EIgG associated with increased TEARS also caused a depression of Fc receptor-mediated phagocytosis and phorbol myrista te acetate (PMA)-stimulated hydrogen peroxide production. Time course experiments demonstrated that the increase in TEARS coincided with the depression of macrophage function, There was no increase in TEARS fol lowing the phagocytosis of IgG-coated erythrocyte ghosts, suggesting t hat hemoglobin iron is involved in the generation of TEARS, The phagoc ytosis of erythrocyte ghosts did not depress macrophage function, Sinc e complement receptor-mediated phagocytosis does not stimulate the res piratory burst, the role of the respiratory burst in causing lipid per oxidation was assessed using the phagocytosis of complement-coated ery throcytes, Phagocytic challenge with complement-coated erythrocytes ca used neither an increase in TEARS nor a depression of macrophage funct ion, However, there was an increase in TEARS when the respiratory burs t was stimulated with PMA following complement receptor-mediated phago cytosis of erythrocytes. These results suggest that hemoglobin iron an d phagocyte-generated oxidants collaborate to cause the depression of macrophage function following EIgG phagocytosis.