STIMULATION BY VASOACTIVE-INTESTINAL-PEPTIDE (VIP) OF PHAGOCYTIC FUNCTION IN RAT MACROPHAGES - PROTEIN-KINASE-C INVOLVEMENT

The action of vasoactive intestinal peptide (VIP) on macrophages has not yet been studied, although there are studies that show an inhibitory action of VIP on lymphocyte functions. The present study shows that VIP in a range from 10(-12) to 10(-7) M increased significantly the phagocytosis and digestion capacities of rat peritoneal macrophages. The most effective concentration of VIP was 10(-9) M followed by 10(-8) M. With respect to the phagocytic capacity, the ingestion of cells (Candida albicans) or inert particles (latex beads) was stimulated significantly with all the concentrations used. The digestion capacity was analyzed through the production of superoxide anion, measured by the reduction of nitroblue tetrazolium (NBT). As with phagocytic capacity, superoxide anion production was increased by VIP in non-stimulated macrophages (incubated without latex beads) and even more in stimulated cells (incubated in the presence of latex beads). The study of the mechanism of action of this neuropeptide showed that protein kinase C (PKC) was activated in the presence of VIP concentrations from 10(-10) to 10(-8) M in a similar way to that found with a specific PKC activator such as phorbol myristate acetate (PMA, 50 ng/ml). PMA also stimulated significantly the phagocytosis and digestion capacities of rat macrophages. By contrast, a PKC inhibitor, retinal (20 muM), decreased significantly the phagocytosis and digestion capacities. These data show that VIP could stimulate these macrophage functions through PKC activation.