IMMUNOTOXICOLOGY OF CIGARETTE-SMOKE CONDENSATES - SUPPRESSION OF MACROPHAGE RESPONSIVENESS TO INTERFERON-GAMMA

We have investigated systematically the effects of short-term exposure to main stream cigarette smoke condensates (CSC-MS) on basal and indu cible functional capacities of murine peritoneal exudate macrophages. Macrophages treated with CSC-MS form granules that fluoresce orange un der blue excitation, consistent with the speculation that they are pol ycyclic aromatic hydrocarbons (PAH). CSC-MS selectively suppressed int erferon gamma IFN gamma) induction of four macrophage functional capac ities: enhanced phagocytosis of immunoglobulin-opsonized sheep red blo od cells, TPA-induced H2O2 production, class II major histocompatibili ty complex expression, and nitric oxide synthesis. In contrast, two ma crophage functions that are not induced by IFN gamma, basal electron t ransport and LPS-induced TNF alpha production, were enhanced by treatm ent with CSC-MS. These results suggest that the suppressive effects of CSC-MS on macrophage responsiveness were selective and were not due t o nonspecific inhibition of general functions such as RNA or protein s ynthesis. Since macrophage responsiveness to IFN gamma can result in i nduction of functional capacities that are fundamental to immunity, th e data suggest that CSC-MS maybe deleterious to the general health of the smoker. (C) 1998 Academic Press.