Effects of Malathion on Humoral Immunity and Macrophage Function in Mast Cell-Deficient Mice

Malathion, when administered at noncholinergic doses, was previously shown to enhance the humoral immune response to a T-dependent antigen, sheep red blood cells (SRBC), and macrophage function. In addition, malathion was shown to cause mast cell degranulation. The hypothesis that mast cells contribute to the observed alterations in humoral immunity and macrophage function was determined by examination of the effects of acute administration of malathion to mast cell-deficient mice on macrophage function and the generation of a humoral immune response to SRBC. Initial studies in two strains of mast cell-deficient mice (6-7 weeks old) indicated that oral administration of malathion reduced macrophage function in these mice, but enhanced macrophage function in the wild-type strain. Because both strains reacted in a similar fashion and the defect in the WBB6F1-W/WV strain allowed reconstitution, further studies were conducted with this strain. Exposure of either wild-type mice or mast cell-deficient mice with reconstituted with bone marrow-derived mast cells (BMMC) from the wild-type mice to malathion enhanced macrophage function and the production of circulating IgM, but not IgG, antibodies to SRBC on Days 3 and 5 after immunization. In contrast, administration of malathion to older mast cell-deficient mice suppressed the generation of IgM and IgG antibodies to SRBC on Days 3 and 5 after immunization, but did not affect macrophage function. In summary, the results presented indicate that the presence of mast cells was necessary for the increases in macrophage function and humoral immunity observed after acute oral administration of malathion to mice.