Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2

摘要: We have investigated whether the signaling protein phospholipase D is implicated in leukocyte cell motility. Treating differentiated HL-60 cells with small interfering RNAs (siRNAs), to deplete endogenous expression of PLD1 isoform, led an abolishment basal chemokinesis that could not be rescued chemoattractants ENA-78, FMLP, and IL-8. Transient overexpression increased both chemotaxis toward IL-8 FMLP but ENA-78. Chemokinesis was mediated by enzymatic activity PLD1, chemotactic response was, because a lipase-inactive mutant (PLD1-K830R) negated all chemokine-induced potentiating actions vitro. Gene silencing other mammalian PLD2, also migration arrest, whereas ENA-78 selectively PLD2 overexpressing myc-pcDNA-PLD2 construct. Thus, differentially activated CXCR-1, CXCR-2 (and possibly CXCR-1) mediates activation. Finally, immunofluorescence microscopy showed isoforms were associated polarity directionality concomitantly adhesion F-actin polymerization These data represent first demonstration involvement PLD its chemokines key physiologic process migration.