MOLECULAR MECHANISMS OF SIGNAL TRANSDUCTION IN MONONUCLEAR PHAGOCYTES

Over the past several years we have investigated the molecular mechani sms which mediate the responsiveness of mononuclear phagocytes to phys iologically relevant stimuli. The actions of interferon-gamma (IFN-gam ma) involve the rapid activation of a Na+/H+ antiport and the delayed activation of transduction mechanisms by chemoattractants. Bacterial l ipopolysaccharide (LPS) affects the levels of several transduction mol ecules in macrophages such as intracellular H+ and Ca2+ and cyclic nuc leotides and stimulates protein kinase C activity. The chemoattractant platelet-activating factor (PAF) is a transient calcium-mobilizing ag onist for macrophages. Termination of its cellular effects appears to involve stimulated prostanoid secretion and the resulting increase in cAMP levels. Our data indicate a role for the interplay of these agoni sts in regulation of molecules important for signal transduction in ma crophages.