ACTIVATION OF PHOSPHOLIPASE-D IS AN EARLY EVENT IN INTEGRIN-MEDIATED SIGNALING LEADING TO PHAGOCYTOSIS IN HUMAN NEUTROPHILS

Integrin receptors on human neutrophils mediate adhesion and phagocyto sis. These functions are linked to a signal-transduction cascade that rearranges the cytoskeleton. The intention of this study was to clarif y how activation of phospholipase D (PLD) is coupled to the complement receptor three (CR3, CD18/CD11b)-mediated ingestion process. Carboben zyloxy-leucine-tyrosine-chloromethylketone (zLYCK) inhibited PLD activ ation induced by complement-opsonized yeast particles (COYP) by 39%. P hagocytosis of these panicles was reduced by zLYCK to the same extent. Anti-CD18-antibodies bound to protein A-positive Staphylococcus aureu s bacteria induced a significant PLD activation. These particles were not ingested which implicates that CR-mediated ingestion per se is not required to induce PLD activity. Cytochalasin B-treatment, which bloc ks actin reorganization, partly reduced COYP-mediated PLD activity, bu t had no effect on activity caused by anti-CD18-coated particles. This excludes activation of PLD to be a secondary event, but rather an ear ly signal in the phagocytic uptake prior to actin reorganization. Thes e data suggest an important and early role for PLD in integrin-mediate d phagocytosis.