Regulation of oscillations in filamentous actin content in polymorphonuclear leukocytes stimulated with leukotriene B-4 and platelet-activating factor

Stimulation of neutrophils with LTB4 or PAF results in the production of a rapidly oscillating actin polymerization/depolymerization response. Treatme nt of neutrophils with inhibitors of PKC prior to stimulation with ligand r esulted in a masking of the F-actin oscillations. Because myosin has been s hown to be a substrate for neutrophil PKC, this protein was investigated as a potential downstream mediator of F-actin oscillations. Stimulation of ne utrophils with LTB4 resulted in myosin light chain being serine phosphoryla ted in a PKC-dependent manner. This phosphorylation was shown to occur in a manner that is kinetically distinct from the myosin phosphorylation induce d by FMLP, a potent activator of actin polymerization that alone does not i nduce F-actin oscillations. Additionally, disruption of intracellular actin -myosin interactions resulted in inhibition of LTB4- as well as PAF-induced F-actin oscillations. These data suggest that PKC and downstream phosphory lation of myosin as well as actin-myosin interaction may play roles in medi ating the production of neutrophil F-actin oscillations, (C) 1999 Academic Press.