Rapid oscillations of actin polymerization/depolymerization in polymorphonuclear leukocytes stimulated by leukotriene B4 and platelet-activating factor.

Abstract

We previously showed that activation of polymorphonuclear leukocytes by leukotriene B4 (LTB4) and platelet-activating factor produces a rapidly oscillating actin polymerization/depolymerization response. In this study, we show that 1) oscillations are not due to the stimulated cyclic release of autocoids that could bind to cell surface receptors and activate subsequent cycles; 2) oscillations are not related to oscillations of ligand binding; and 3) the particular kinetic pattern is a property of the receptor, not of the binding constants of the ligand. The major conclusion of these studies is that the oscillations are a property of the intrinsic signaling pathways triggered by these chemoattractants. We also questioned whether increased actin nucleation activity was induced by LTB4 and found that, although LTB4 induced a transient actin nucleation response, there was not a direct correlation between oscillations of the actin polymerization/depolymerization and the actin nucleation activity. This suggests that processes other than actin nucleation, such as release of monomeric actin from monomer sequestering proteins and regulation of depolymerization, are likely to be involved.