Contribution of mast cell mediators to alterations in macrophage function after malathion administration.

Previous studies showed that acute administration of noncholinergic doses of malathion increased macrophage function and the generation of a primary humoral immune response to a T-dependent antigen and caused mast cell degranulation. Recent studies using mast cell-deficient mice showed that the presence of mast cells was necessary for the increase in macrophage function observed after oral administration of malathion, and reconstitution with bone marrow-derived mast cells restored the ability of malathion to increase macrophage function. In the present study, the contribution of mast cell mediators to alterations in macrophage function after oral administration of malathion was examined. Controls in this study included the effect of the agent to be examined on resident peritoneal macrophages and macrophages elicited with pristane, an agent that can stimulate macrophages in the absence of mast cells. Coadministration of intraperitoneal cromolyn, a stabilizer of mast cell membranes, with oral malathion blocked the ability of malathion to increase macrophage function as measured by the generation of respiratory burst activity, the phagocytosis of opsonized yeast, and the production of cathepsin D. On the other hand, administration of cromolyn to mice whose macrophage function was stimulated with pristane did not affect the observed increases in macrophage function. As oral administration of malathion caused histamine release, the ability of a histamine receptor antagonist, pyrilamine, to alter the response of peritoneal macrophages to oral administration of malathion was also examined. Intraperitoneal administration of pyrilamine partially blocked the effects of oral administration of malathion on peritoneal macrophage function, but did not affect the function of resident or pristane-elicited peritoneal macrophages. These data suggest that mediators from mast cells contribute to the elevation in macrophage function observed after oral malathion administration.