SEARCH:   Advanced

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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 27, 2006 Accepted June 24, 2006 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* Cell Biology and Physiology, Wright State University School of Medicine, Dayton, Ohio * Corresponding author; email: julian.cambronero{at}wright.edu. 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), in order 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 towards IL-8 and FMLP, but not towards ENA-78. Chemokinesis was not mediated by PLD1’ s enzymatic activity, but the chemotactic response was, as a lipase-inactive mutant (PLD1-K830R) negated all chemokine-induced potentiating actions; and since 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-60s overexpressing a myc-pdDNA-PLD2 construct. Thus, PLD1 is differentially activated by CXCR-1, while 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 activities towards chemokines in the key physiological process of leukocyte migration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Itoh, J. Hasegawa, K. Tsujita, Y. Kanaho, and T. Takenawa The Tyrosine Kinase Fer Is a Downstream Target of the PLD-PA Pathway that Regulates Cell Migration Sci. Signal., September 8, 2009; 2(87): ra52 - ra52. [Abstract] [Full Text] [PDF] R. Stillie, S. M. Farooq, J. R. Gordon, and A. W. Stadnyk The functional significance behind expressing two IL-8 receptor types on PMN J. Leukoc. Biol., September 1, 2009; 86(3): 529 - 543. [Abstract] [Full Text] [PDF] A. Nishikimi, H. Fukuhara, W. Su, T. Hongu, S. Takasuga, H. Mihara, Q. Cao, F. Sanematsu, M. Kanai, H. Hasegawa, et al. Sequential Regulation of DOCK2 Dynamics by Two Phospholipids During Neutrophil Chemotaxis Science, April 17, 2009; 324(5925): 384 - 387. [Abstract] [Full Text] [PDF] Y. C. Chae, J. H. Kim, K. L. Kim, H. W. Kim, H. Y. Lee, W. D. Heo, T. Meyer, P.-G. Suh, and S. H. Ryu Phospholipase D Activity Regulates Integrin-mediated Cell Spreading and Migration by Inducing GTP-Rac Translocation to the Plasma Membrane Mol. Biol. Cell, July 1, 2008; 19(7): 3111 - 3123. [Abstract] [Full Text] [PDF] I. Gorshkova, D. He, E. Berdyshev, P. Usatuyk, M. Burns, S. Kalari, Y. Zhao, S. Pendyala, J. G. N. Garcia, N. J. Pyne, et al. Protein Kinase C-{epsilon} Regulates Sphingosine 1-Phosphate-mediated Migration of Human Lung Endothelial Cells through Activation of Phospholipase D2, Protein Kinase C-{zeta}, and Rac1 J. Biol. Chem., April 25, 2008; 283(17): 11794 - 11806. [Abstract] [Full Text] [PDF] M. Uddin, G. Seumois, L. C. Lau, P. Rytila, D. E. Davies, and R. Djukanovic Enhancement of neutrophil function by the bronchial epithelium stimulated by epidermal growth factor Eur. Respir. J., April 1, 2008; 31(4): 714 - 724. [Abstract] [Full Text] [PDF] S. O. Carrigan, D. B. S. Pink, and A. W. Stadnyk Neutrophil transepithelial migration in response to the chemoattractant fMLP but not C5a is phospholipase D-dependent and related to the use of CD11b/CD18 J. Leukoc. Biol., December 1, 2007; 82(6): 1575 - 1584. [Abstract] [Full Text] [PDF] J. Gomez-Cambronero, M. Di Fulvio, and K. Knapek Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell adhesion and chemotaxis J. Leukoc. Biol., August 1, 2007; 82(2): 272 - 281. [Abstract] [Full Text] [PDF] N. Lehman, B. Ledford, M. Di Fulvio, K. Frondorf, L. C. McPhail, and J. Gomez-Cambronero Phospholipase D2-derived phosphatidic acid binds to and activates ribosomal p70 S6 kinase independently of mTOR FASEB J, April 1, 2007; 21(4): 1075 - 1087. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020