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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3564-3572. Prepublished online as a Blood First Edition Paper on July 27, 2006; DOI 10.1182/blood-2006-02-005959. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-005959v1 108/10/3564    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lehman, N. Articles by Gomez-Cambronero, J. Search for Related Content PubMed PubMed Citation Articles by Lehman, N. Articles by Gomez-Cambronero, J. Related Collections Phagocytes Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2 Nicholas Lehman, Mauricio Di Fulvio, Nicholas McCray, Isabel Campos, Farnaz Tabatabaian, and Julian Gomez-Cambronero From Cell Biology and Physiology, Wright State University School of Medicine, Dayton, OH. 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 the PLD1 isoform, led to an abolishment of basal chemokinesis that could not be rescued with chemoattractants ENA-78, FMLP, and IL-8. Transient overexpression of PLD1 increased both chemokinesis and chemotaxis toward IL-8 and FMLP but not toward ENA-78. Chemokinesis was not mediated by the enzymatic activity of PLD1, but the chemotactic response was, because a lipase-inactive mutant (PLD1-K830R) negated all chemokine-induced potentiating actions and because IL-8 and FMLP increased activity in vitro. Gene expression silencing of the other mammalian isoform, PLD2, also led to cell migration arrest, whereas ENA-78 selectively increased endogenous PLD2 activity and chemotaxis of HL-60 cells overexpressing a myc-pcDNA-PLD2 construct. Thus, PLD1 is differentially activated by CXCR-1, whereas CXCR-2 (and possibly CXCR-1) mediates PLD2 activation. Finally, immunofluorescence microscopy showed that both isoforms were associated with cell polarity and directionality concomitantly with adhesion and F-actin polymerization in response to IL-8. These data represent the first demonstration of the involvement of PLD and its enzymatic activity toward chemokines in the key physiologic process of leukocyte migration. 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