Environmental chemical-induced macrophage dysfunction

Abstract

Immunomodulation by environmental chemical contaminants and the role immune parameters play in toxicity and risk assessment studies is of increasing concern. Although considerable evidence has indicated that various xenobiotics may be immunosuppressive, little attention has been directed toward ascertaining a specific cellular locus which could be responsible for the impaired immune responsiveness. Since previous studies had suggested a macrophage defect in xenobiotic-induced immunosuppression and since macrophages are integral components of an immune response, an in-depth evaluation of macrophage function was conducted in xenobiotic-exposed mice. Macrophages isolated from mice receiving PCB, HCB, and dieldrin had no alteration in their in vitro O2 consumption while at rest or during phagocytosis. In addition, no alteration in in vitro phagocytic activity, phagocytic capacity or microbicidal activity was demonstrated. However, a significant impairment in the in vivo phagocytic clearance of a labelled antigen and an altered tissue distribution of the antigen was observed and was, perhaps, related, in part, to a significant decrease in serum fibronectin, an opsonic alpha 2 surface-binding glycoprotein. Furthermore, animals exposed to HCB and dieldrin, but not to PCB, had a profound decrease in their resistance to a challenge tumor cell implant which was related to a select alteration in tumor cell killing. The adherent spleen cells from HCB-treated mice had a profound suppression in their tumoricidal activity which was in contrast to dieldrin-treated mice, where the target cell type appeared to be the nonadherent cells. However, although dieldrin-exposed adherent cells (macrophages ?) did nt appear to have an altered tumoricidal capacity, all four macrophage types isolated from dieldrin-treated mice had a significantly impaired ability to process a cellular antigen. Splenic and alveolar macrophages appeared to be the most sensitive cell types to dieldrin. The present studies suggest that macrophage dysfunction may be an integral part of xenobiotic-induced immunosuppression and that the effector but not affector component of macrophage function may be the site of alteration.