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* Department of Pediatrics, Division of Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206;
Department of Pharmacology, University of Colorado and Health Sciences Center, Aurora, CO 80045;
Department of Hematology, Rigshospitalet-4042, Copenhagen, Denmark;
Department of Medicine and Pathology, University of Colorado and Health Sciences Center, Aurora, CO 80045; and
¶ Department of Pediatrics, University of Colorado and Health Sciences Center, Aurora, CO 80045
Lysophosphatidylcholine has been shown to enhance neutrophil functions through a mechanism involving the G protein-coupled receptor G2A. Recent data support an indirect effect of lysophosphatidylcholine on G2A rather than direct ligand binding. These observations prompted the hypothesis that other lysophospholipids (lyso-PLs) may also signal for human neutrophil activation through G2A. To this end, 1-oleoyl-2-hydroxy-sn-glycero-3-[phospho-L-choline], but also C18:1/OH lyso-PLs bearing the phosphoserine and phosphoethanolamine head groups, presented on albumin, were shown to signal for calcium flux in a self- and cross-desensitizing manner, implicating a single receptor. Blocking Abs to G2A inhibited calcium signaling by all three lyso-PLs. Furthermore, inhibition by both pertussis toxin and U-73122 established signaling via the G
i/phospholipase C pathway for calcium mobilization. Altered plasma membrane localization of G2A has been hypothesized to facilitate signaling. Accordingly, an increase in detectable G2A was demonstrated by 1 min after lyso-PL stimulation and was followed by visible patching of the receptor. Western blotting showed that G2A resides in the plasma membrane/secretory vesicle fraction and not in neutrophil primary, secondary, or tertiary granules. Enhanced detection of G2A induced by lyso-PLs was paralleled by enhanced detection of CD45, confirming mobilization of the labile secretory vesicle pool. Together, these data show that lyso-PLs bearing various head groups redundantly mobilize G2A latent within secretory vesicles and result in G2A receptor/Gi/phospholipase C signaling for calcium flux in neutrophils.
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.
1 This work was supported by National Institutes of Health Grants AI058228, HL34303, and GM61031.
2 Address correspondence and reprint requests to Dr. Donna L. Bratton, National Jewish Medical and Research Center, 1400 Jackson Street, Room D506, Denver, CO 80206. E-mail address: brattond{at}njc.org
3 Abbreviations used in this paper: lyso-PL, lysophospholipid; GPCR, G protein-coupled receptor; lyso-PA, lysophosphatidic acid; lyso-PC, lysophosphatidylcholine; lyso-PE, lysophosphatidylethanolamine; lyso-PS, lysophosphatidylserine; PAF, platelet-activating factor; PLA2, phospholipase A2; PLC, phospholipase C.
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  P. J. Ojala, T. E. Hirvonen, M. Hermansson, P. Somerharju, and J. Parkkinen Acyl chain-dependent effect of lysophosphatidylcholine on human neutrophils J. Leukoc. Biol., December 1, 2007; 82(6): 1501 - 1509. [Abstract] [Full Text] [PDF]
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