In vitro reversibility of cadmium-induced inhibition of phagocytosis

Abstract

Cadmium chloride, administered chronically in the drinking water of CBA/H mice, produced a delayed clearance of particles and soluble material bearing Fc fragments (D. W. Knutson, D. L. Vredevoe, K. R. Aoki, and L. Levy, 1980, Immunology, 40, 17-26; D. L. Vredevoe, L. Levy, D. Knutson, G. Cook, and P. Cohen, 1985, Environ. Res. 37, 373-382). The inhibition was reversed upon removal of the cadmium from the water, even though a tissue load of cadmium persisted. An in vitro system was developed to analyze the mechanism of the inhibition. Binding and ingestion of sheep red blood cells (E) treated with IgG (for measurement of Fc receptor activity) or IgM and complement (C) (for measurement of complement receptor activity) were studied in resident and elicited murine peritoneal macrophages in vitro. Elicited macrophages provided the most definitive test system. With this system, there was significant inhibition of ingestion of E-IgG and E-IgMC. Binding of both types of erythrocytes was not inhibited, except at the highest concentration (10(-4) M) of CdCl2 at which binding of only E-IgMC was affected. These effects were reversible upon removal of cadmium. Migration of Fc and C receptors on the macrophage surface was not significantly affected by cadmium. In general, cadmium did not alter the expression or the binding of Fc or C receptors on macrophages. The mechanism for delayed clearance appears to be due to inhibited internalization of the particles. This is consistent with the interpretation that cadmium is a membrane active agent.