期刊
JOURNAL OF IMMUNOLOGY
卷 178, 期 10, 页码 6540-6548出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.10.6540
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- NHLBI NIH HHS [HL34303] Funding Source: Medline
- NIAID NIH HHS [AI058228] Funding Source: Medline
- NIGMS NIH HHS [GM61031] Funding Source: Medline
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 b oth pertussis toxin and U-73122 established signaling via the G alpha/phospholipase C pathway for calcium mobilization. Alteredplasma 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/G alpha/phospholipase C signaling for calcium flux in neutrophils. The Journal of Immunology, 2007,178: 6540-6548.
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