Activation of phospholipase D is an early event in integrin-mediated signalling leading to phagocytosis in human neutrophils.
Integrin receptors on human neutrophils mediate adhesion and phagocytosis. These functions are linked to a signal-transduction cascade that rearranges the cytoskeleton. The intention of this study was to clarify how activation of phospholipase D (PLD) is coupled to the complement receptor three (CR3, CD18/CD11b)-mediated ingestion process. Carbobenzyloxy-leucine-tyrosine-choloromethylketone (zLYCK) inhibited PLD activation induced by complement-opsonized yeast particles (COYP) by 39%. Phagocytosis of these particles was reduced by zLYCK to the same extent. Anti-CD18-antibodies bound to protein A-positive Staphylococcus aureus 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 blocks actin reorganization, partly reduced COYP-mediated PLD activity, but had no effect on activity caused by anti-CD18-coated particles. This excludes activation of PLD to be a secondary event, but rather an early signal in the phagocytic uptake prior to actin reorganization. These data suggest an important and early role for PLD in integrin-mediated phagocytosis.
Serrander
L
L
Department of Medical Microbiology University of Linköping, Sweden.
Fällman
M
M
Stendahl
O
O
D000199:Actins / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology* / Q000502:physiology; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000502:physiology*; D010739:Phospholipase D / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000199:Actins; D000590:Amino Acid Chloromethyl Ketones; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D003571:Cytochalasin B; C070517:carbobenzyloxyleucyl-tyrosine chloromethyl ketone; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium