Effect of phagocytosis of erythrocytes and erythrocyte ghosts on macrophage phagocytic function and hydrogen peroxide production.
Our previous studies have shown that an in vivo phagocytic challenge with IgG-coated erythrocytes can depress Kupffer cell complement and Fc receptor function, as well as decrease the survival rate following endotoxemia and bacteremia. In an effort to better understand the mechanism underlying these in vivo findings, the present study evaluated the in vitro effects of a phagocytic challenge with either IgG-coated erythrocytes (EIgG) or erythrocyte ghosts (GIgG) on macrophage phagocytic and respiratory burst activity. Elicited rat peritoneal macrophage (PM) monolayers were challenged with varying doses of EIgG, then the noninternalized EIgG were lysed hypotonically and the monolayers incubated for an additional hour prior to determining phagocytic function and PMA-stimulated hydrogen peroxide production. Challenge of PM with 1 x 10(6) EIgG per well had no effect, but challenge with 1 x 10(7) or 1 x 10(8) EIgG per well caused a dose-dependent depression of phagocytic function or hydrogen peroxide production. GIgG were formed by hypotonically lysing EIgG bound to PM at 4 degrees C. The bound GIgG were phagocytized during a subsequent incubation at 37 degrees C. Challenge with GIgG depressed phagocytic function only with the highest challenge dose tested (1 x 10(8) per well) and did not depress hydrogen peroxide production. The observation that prior phagocytic challenge with EIgG depressed macrophage function to a greater extent than challenge with GIgG supports our previous in vivo observations. Furthermore, these studies suggest that the internalization of erythrocyte contents, and not phagocytosis per se, plays an important role in determining macrophage host defense function.
Commins
L M
LM
Department of Physiology and Cell Biology, Albany Medical College, New York 12208.
Loegering
D J
DJ
Gudewicz
P W
PW
D000818:Animals; D004910:Erythrocyte Membrane; D004912:Erythrocytes; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D010587:Phagocytosis; D051381:Rats; D011919:Rats, Inbred Strains
D007074:Immunoglobulin G; D006861:Hydrogen Peroxide