Release of lysophospholipid 'find-me' signals during apoptosis requires the ATP-binding cassette transporter A1.
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.
Department of Internal Medicine I, University of Tuebingen, Tuebingen, Germany.
Christoph
C
Peter
Michaela
M
Waibel
Hildegard
H
Keppeler
Rainer
R
Lehmann
Guowang
G
Xu
Anna
A
Halama
Jerzy
J
Adamski
Klaus
K
Schulze-Osthoff
Sebastian
S
Wesselborg
Kirsten
K
Lauber
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002633:Chemotaxis; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008244:Lysophosphatidylcholines; D034741:RNA, Small Interfering