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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1611-1617. Prepublished online as a Blood First Edition Paper on May 9, 2006; DOI 10.1182/blood-2005-11-012328. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2005-11-012328v1 108/5/1611    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 Elliott, J. I Articles by Higgins, C. F Search for Related Content PubMed PubMed Citation Articles by Elliott, J. I Articles by Higgins, C. F Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 15, 2005 Accepted April 24, 2006 Phosphatidylserine exposure in B lymphocytes: a role for lipid packing James I Elliott*, Alessandro Sardini, Joanne C Cooper, Denis R Alexander, Suzel Daventure, Giovanna Chimini, and Christopher F Higgins MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, UK Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK Centre d'Immunologie de Marseille-Luminy, Parc Scientifique et Technologique de Luminy, France * Corresponding author; email: james.elliott{at}csc.mrc.ac.uk. Plasma membrane lipids are usually distributed asymmetrically, with phosphatidylserine (PS) confined to the inner leaflet. PS exposure at the outer leaflet occurs early in apoptosis, but is also constitutive on some non-apoptotic cell populations where it plays a role in cell signalling. How PS is transported (" flopped" ) to the cell surface is unknown. Contrary to previous reports that normal murine B lymphocytes lack lipid asymmetry, we show that PS is normally restricted to the inner leaflet of these cells. PS exposure on normal B cells did, however, occur spontaneously ex vivo. Consistent with the hypothesis that loss of PS asymmetry is regulated by CD45, PS is constitutively exposed on viable, CD45-deficient B cells. We show that calcium-stimulated PS exposure in B cells is strain-variable, ABCA1- independent, and is preceded by and dependent on a decrease in lipid packing. This decrease in lipid packing is concomitant with cell shrinkage and consequent membrane distortion. Both are potently inhibited by blockers of volume-regulatory K+ and Cl- ion channels. Thus, changes in plasma membrane organisation precede PS translocation. The data suggest a model in which PS redistribution may occur by a translocase-independent mechanism at energetically favourable sites of membrane perturbation where lipid packing is decreased. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. G. Blankenberg Imaging the Molecular Signatures of Apoptosis and Injury with Radiolabeled Annexin V Proceedings of the ATS, August 15, 2009; 6(5): 469 - 476. [Abstract] [Full Text] [PDF] S. Hong, N. Schwarz, A. Brass, M. Seman, F. Haag, F. Koch-Nolte, W. P. Schilling, and G. R. Dubyak Differential Regulation of P2X7 Receptor Activation by Extracellular Nicotinamide Adenine Dinucleotide and Ecto-ADP-Ribosyltransferases in Murine Macrophages and T Cells J. Immunol., July 1, 2009; 183(1): 578 - 592. [Abstract] [Full Text] [PDF] S. R. Stowell, S. Karmakar, C. M. Arthur, T. Ju, L. C. Rodrigues, T. B. Riul, M. Dias-Baruffi, J. Miner, R. P. McEver, and R. D. Cummings Galectin-1 Induces Reversible Phosphatidylserine Exposure at the Plasma Membrane Mol. Biol. Cell, March 1, 2009; 20(5): 1408 - 1418. [Abstract] [Full Text] [PDF] S. C. Frasch, K. Z. Berry, R. Fernandez-Boyanapalli, H.-S. Jin, C. Leslie, P. M. Henson, R. C. Murphy, and D. L. Bratton NADPH Oxidase-dependent Generation of Lysophosphatidylserine Enhances Clearance of Activated and Dying Neutrophils via G2A J. Biol. Chem., November 28, 2008; 283(48): 33736 - 33749. [Abstract] [Full Text] [PDF] F. G. Blankenberg In Vivo Detection of Apoptosis J. Nucl. Med., June 1, 2008; 49(Suppl_2): 81S - 95S. [Abstract] [Full Text] [PDF] S. R. J. Taylor, M. Gonzalez-Begne, S. Dewhurst, G. Chimini, C. F. Higgins, J. E. Melvin, and J. I. Elliott Sequential Shrinkage and Swelling Underlie P2X7-Stimulated Lymphocyte Phosphatidylserine Exposure and Death J. Immunol., January 1, 2008; 180(1): 300 - 308. [Abstract] [Full Text] [PDF] D. Smrz, L. Draberova, and P. Draber Non-apoptotic Phosphatidylserine Externalization Induced by Engagement of Glycosylphosphatidylinositol-anchored Proteins J. Biol. Chem., April 6, 2007; 282(14): 10487 - 10497. [Abstract] [Full Text] [PDF]

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