BRIEF REPORT Release of lysophospholipid ‘find-me’ signals during apoptosis requires the ATP-binding cassette transporter A1 CHRISTOPH PETER 1,7, *, MICHAELA WAIBEL 1, *, HILDEGARD KEPPELER 1 , RAINER LEHMANN 2 , GUOWANG XU 5 , ANNA HALAMA 6 , JERZY ADAMSKI 6 , KLAUS SCHULZE-OSTHOFF 3 , SEBASTIAN WESSELBORG 1,7 , & KIRSTEN LAUBER 1,4 1 Department of Internal Medicine I, University of Tuebingen, Tuebingen, Germany, 2 Department of Internal Medicine IV, University of Tuebingen, Tuebingen, Germany, 3 Interfaculty Institute for Biochemistry, University of Tuebingen, 4 Department of Radiation Oncology, Ludwig-Maximilians-University, Munich, Germany, 5 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China, 6 Genome Analysis Centre, Institute of Experimental Genetics, Helmholtz Center Munich, Germany, and 7 Institute of Molecular Medicine, Heinrich-Heine-University, Du ¨sseldorf, Germany (Submitted 28 June 2012; accepted 5 July 2012) Abstract Efficient engulfment of apoptotic cells is essential in multi-cellular organisms in order to prevent inflammatory responses. Apoptotic cells secure this process by releasing ‘find-me’ signals for the attraction of phagocytes. A major ‘find-me’ signal liberated from apoptotic cells is lysophosphatidylcholine (LPC). So far, however, the mechanisms underlying LPC release are poorly understood. In this study, we demonstrate that pharmacological inhibition and RNAi-mediated knock-down of the lipid transporter ABCA1 in apoptotic cells completely abolished phagocyte attraction. Moreover, ectopic expression of ABCA1 significantly enhanced monocyte migration to supernatants of apoptotic cells. Hence, ABCA1 represents a novel regulator of LPC release during apoptosis. Keywords: Apoptosis, chemotaxis, ‘find-me’ signal, lysophosphatidylcholine, ATP-binding cassette transporter Abbreviations: ABC-transporter, ATP-binding cassette transporter, BEL, bromoeenollactone, casp3, caspase-3, iPLA 2 , Ca 2þ -independent phospholipase A 2 , Glyb, glyburide, HDL, high density lipoprotein, LPC, lysophosphatidylcholine, MCF7 casp3 , MCF7 cell transgenic for caspase 3, PS, phosphatidylserine, qRT-PCR, quantitative real-time RT-PCR, SDF-1, stromal cell-derived factor 1 Introduction During development and daily tissue regeneration billions of cells die by apoptosis. Under physiological conditions, these cells are swiftly engulfed by neighbor- ing cells or professional phagocytes. If the process of corpse elimination fails, apoptotic cells undergo secondary necrosis and release potentially cytotoxic and antigenic intracellular contents that can cause persistent auto-inflammatory disorders. Conse- quently, autoimmune diseases, such as systemic lupus erythematosus, have been linked to defective clearance of apoptotic cells [1]. To guarantee their timely removal, apoptotic cells have to be recognized by professional or semi- professional phagocytes. This recognition is mediated by ‘eat-me’ signals on the surface of apoptotic cells, including phosphatidylserine (PS) [2]. The signaling events that mediate prey cell internalization were first identified in C. elegans, where two partially redundant signaling cassettes regulate engulfment. CED-2, CED-5 and CED-12 with their mammalian homologues CrkII, DOCK180, ELMO act in the first pathway [3]. CED-1, CED-6, CED-7 constitute the second cassette, in which CED-1 or its mammalian Correspondence: Kirsten Lauber, Department of Radiation Oncology, Ludwig-Maximilians-University, Munich, Germany. E-mail: kirsten.lauber@med.uni-muenchen.de *C.P. and M.W. equally contributed to the work. Autoimmunity, 2012; Early Online: 1–6 q Informa UK, Ltd. ISSN 0891-6934 print/1607-842X online DOI: 10.3109/08916934.2012.719947 Autoimmunity Downloaded from informahealthcare.com by Martin Herrmann on 10/16/12 For personal use only.