LYSOSOMOTROPIC AGENTS AMELIORATE MACROPHAGE DYSFUNCTION FOLLOWING THEPHAGOCYTOSIS OF IGG-COATED ERYTHROCYTES - A ROLE FOR LIPID-PEROXIDATION

Phagocytosis of IgG-coated erythrocytes (EIgG) can depress several mac rophage functions. Our previous studies have suggested that this macro phage dysfunction may be due to an oxidative stress caused by the inte raction of hemoglobin-derived iron with superoxide and/or hydrogen per oxide. Since lysosomotropic agents are capable of altering iron handli ng by macrophages, the present study evaluated the ability of these ag ents to prevent the macrophage dysfunction and lipid peroxidation caus ed by a phagocytic challenge with EIgG. Elicited rat peritoneal macrop hages showed a depression of PMA-stimulated hydrogen peroxide producti on, calcium ionophore-stimulated arachidonate release and Fc receptor- mediated phagocytosis. The lysosomotropic agents; chloroquine, quinacr ine, ammonium chloride and methylamine all prevented the depression of hydrogen peroxide production and arachidonate release but did not alt er the depression of phagocytic function. These agents also prevented the increase in lipid peroxidation products caused by a phagocytic cha llenge with EIgG. These results suggest that the ability of lysosomotr opic agents to prevent some aspects of macrophage dysfunction after a phagocytic challenge may be due to their ability to block the oxidativ e stress caused by the challenge.