HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 28, 26612-26621, July 15, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/28/26612    most recent M501359200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hinkovska-Galcheva, V. Articles by Shayman, J. A. Search for Related Content PubMed PubMed Citation Articles by Hinkovska-Galcheva, V. Articles by Shayman, J. A. Social Bookmarking                      What's this?

Ceramide 1-Phosphate, a Mediator of Phagocytosis^*

Vania Hinkovska-Galcheva, Laurence A. Boxer, Andrei Kindzelskii, Miki Hiraoka¶, Akira Abe¶, Sravan Goparju||, Sarah Spiegel||, Howard R. Petty**, and James A. Shayman¶

From the Department of Pediatrics, Division of Hematology/Oncology, Department of Ophthalmology and Visual Science, ^¶Department of Internal Medicine, Division of Nephrology, and ^||Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298 and ^**Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109

The agonist-stimulated metabolism of membrane lipids produces potent second messengers that regulate phagocytosis. We studied whether human ceramide kinase (hCERK) activity and ceramide 1-phosphate formation could lead to enhanced phagocytosis through a mechanism involving modulation of the membrane-structural order parameter. hCERK was stably transfected into COS-1 cells that were stably transfected with the FcRIIA receptor. hCERK-transfected cells displayed a significant increase in phagocytic index in association with increased ceramide kinase activation and translocation to lipid rafts after activation with opsonized erythrocytes. When challenged with opsonized erythrocytes, hCERK-transfected cells increased phagocytosis by 1.5-fold compared with vector control and simultaneously increased ceramide 1-phosphate levels 2-fold compared with vector and unstimulated control cells. Control and hCERK-transfected cells were subjected to cellular fractionation. Utilizing an antibody against hCERK, we observed that CERK translocates during activation from the cytosol to a lipid raft fraction. The plasma membrane-structural order parameter of the transfectants was measured by labeling cells with Laurdan. Cells transfected with hCERK showed a higher liquid crystalline order than control cells with stimulation, conditions that are favorable for the promotion of membrane fusion at the sites of phagocytosis. The change in the structural order parameter of the lipid rafts probably contributes to phagocytosis by promoting phagosome formation.

Received for publication, February 4, 2005 , and in revised form, May 13, 2005.

^* This work is supported by National Institutes of Health Grants AI20065 (to L. A. B.) and DK055823 (to J. A. S,) and National Multiple Sclerosis Society grant (to H. R. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: 1150 W. Medical Center Dr., 1560 MSRB II, Ann Arbor, MI 48109-0676.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. E. Kooijman, J. Sot, L.-R. Montes, A. Alonso, A. Gericke, B. de Kruijff, S. Kumar, and F. M. Goni Membrane Organization and Ionization Behavior of the Minor but Crucial Lipid Ceramide-1-Phosphate Biophys. J., June 1, 2008; 94(11): 4320 - 4330. [Abstract] [Full Text] [PDF]

				V. Hinkovska-Galcheva, A. Clark, S. VanWay, J.-B. Huang, M. Hiraoka, A. Abe, M. Borofsky, R. G. Kunkel, T. Shanley, J. A. Shayman, et al. Ceramide kinase promotes Ca2+ signaling near IgG-opsonized targets and enhances phagolysosomal fusion in COS-1 cells J. Lipid Res., March 1, 2008; 49(3): 531 - 542. [Abstract] [Full Text] [PDF]

				C. Graf, B. Zemann, P. Rovina, N. Urtz, A. Schanzer, R. Reuschel, D. Mechtcheriakova, M. Muller, E. Fischer, C. Reichel, et al. Neutropenia with Impaired Immune Response to Streptococcus pneumoniae in Ceramide Kinase-Deficient Mice J. Immunol., March 1, 2008; 180(5): 3457 - 3466. [Abstract] [Full Text] [PDF]

				N. F. Lamour, R. V. Stahelin, D. S. Wijesinghe, M. Maceyka, E. Wang, J. C. Allegood, A. H. Merrill Jr., W. Cho, and C. E. Chalfant Ceramide kinase uses ceramide provided by ceramide transport protein: localization to organelles of eicosanoid synthesis J. Lipid Res., June 1, 2007; 48(6): 1293 - 1304. [Abstract] [Full Text] [PDF]

				S. Spiegel and S. Milstien Functions of the Multifaceted Family of Sphingosine Kinases and Some Close Relatives J. Biol. Chem., January 26, 2007; 282(4): 2125 - 2129. [Full Text] [PDF]

				D. E. Modrak, D. V. Gold, and D. M. Goldenberg Sphingolipid targets in cancer therapy. Mol. Cancer Ther., February 1, 2006; 5(2): 200 - 208. [Abstract] [Full Text] [PDF]

				N. F. Lamour and C. E. Chalfant Ceramide-1-phosphate: The "missing" link in eicosanoid biosynthesis and inflammation Mol. Interv., December 1, 2005; 5(6): 358 - 367. [Abstract] [Full Text] [PDF]