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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2363-2368. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2002-11-3341. This Article Full Text (PDF) All Versions of this Article: 2002-11-3341v1 103/6/2363    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 Mansfield, P. J Articles by Boxer, L. A Search for Related Content PubMed PubMed Citation Articles by Mansfield, P. J Articles by Boxer, L. A Social Bookmarking                   What's this? Submitted November 5, 2002 Accepted November 5, 2003 Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTPS-stimulated polymorphonuclear leukocytes Pamela J Mansfield, Shannon S Carey, Vania Hinkovska-Galcheva, James A Shayman, and Laurence A Boxer* Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA Division of Nephrology, University of Michigan, Ann Arbor, MI, USA * Corresponding author; email: laboxer{at}med.umich.edu. Phospholipase D (PLD) regulates the polymorphonuclear leukocyte (PMN) functions of phagocytosis, degranulation, and oxidant production. Ceramide inhibition of PLD suppresses PMN function. In streptolysin O-permeabilized PMNs PLD was directly activated by GTPS stimulation of ARF and Rho, stimulating release of lactoferrin from specific granules of permeabilized PMNs; PLD activation and degranulation were inhibited by C2-ceramide but not dihydro-C2-ceramide. To investigate the mechanism of ceramide's inhibitory effect on PLD, we used a cell-free system to examine PLD activity and translocation from cytosol to plasma membrane of ARF, PKC and , and RhoA, all of which can activate PLD. GTPS-activated cytosol stimulated PLD activity and translocation of ARF, PKC and , and RhoA when recombined with cell membranes. Prior incubation of PMNs with 10 µM C2-ceramide inhibited PLD activity and RhoA translocation, but not ARF1, ARF6, PKC, or PKC translocation. However, in intact PMNs stimulated with FMLP or permeabilized PMNs stimulated with GTPS, C2-ceramide did not inhibit RhoA translocation. Exogenous RhoA did not restore ceramide-inhibited PLD activity, but bound to membranes despite ceramide treatment. These observations suggest that while ceramide may affect RhoA in some systems, ceramide inhibits PLD through another mechanism, perhaps related to the ability of ceramide to inhibit PIP2 interaction with PLD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] S. Mebarek, H. Komati, F. Naro, C. Zeiller, M. Alvisi, M. Lagarde, A.-F. Prigent, and G. Nemoz Inhibition of de novo ceramide synthesis upregulates phospholipase D and enhances myogenic differentiation J. Cell Sci., February 1, 2007; 120(3): 407 - 416. [Abstract] [Full Text] [PDF] N. Lehman, M. Di Fulvio, N. McCray, I. Campos, F. Tabatabaian, and J. Gomez-Cambronero Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2 Blood, November 15, 2006; 108(10): 3564 - 3572. [Abstract] [Full Text] [PDF] A. Olivera and J. Rivera Sphingolipids and the Balancing of Immune Cell Function: Lessons from the Mast Cell J. Immunol., February 1, 2005; 174(3): 1153 - 1158. [Abstract] [Full Text] [PDF]

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