Mouse and human eosinophils degranulate in response to platelet-activating factor (PAF) and lysoPAF via a PAF-receptor-independent mechanism: evidence for a novel receptor.
Mouse and human eosinophils degranulate in response to platelet-activating factor (PAF) and lysoPAF via a PAF-receptor-independent mechanism: evidence for a novel receptor.
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DOI：
10.4049/jimmunol.0904043
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发表时间：
2010-06-01
期刊：
影响因子：
--
通讯作者：
Rosenberg HF
中科院分区：
文献类型：
--
作者：
Dyer KD;Percopo CM;Xie Z;Yang Z;Kim JD;Davoine F;Lacy P;Druey KM;Moqbel R;Rosenberg HF
血小板活化因子（PAF； 1- o-烷基-2-乙酰- asn -甘油-3-磷脂胆碱）是一种磷脂介质，由活化的巨噬细胞、肥大细胞和嗜碱性细胞释放，可促进病理生理性炎症。嗜酸性粒细胞对PAF的反应是复杂的，尚未完全阐明。我们在这里表明，PAF及其2-去乙酰化代谢物lysoPAF通过一种独立于特征PAF受体（PAFR）的机制促进脱颗粒（嗜酸性粒细胞过氧化物酶的释放）。具体来说，我们证明受体拮抗剂CV-3988和WEB-2086以及百日咳毒素对PAF或lysopaf介导的脱粒没有影响。此外，来自PAFR - / -骨髓祖细胞的培养小鼠嗜酸性粒细胞对PAF和lysoPAF的反应脱粒，其方式与野生型的同类细胞没有区别。除了PAF和lysoPAF外，人嗜酸性粒细胞对溶血磷脂酰胆碱有脱粒反应，但对磷脂酰胆碱、溶血磷脂酰乙醇胺或磷脂酰乙醇胺没有脱粒反应，表现出对具有胆碱头基和sn-2羟基最小取代的磷脂的选择性反应。人嗜酸性粒细胞释放预先形成的细胞因子响应PAF，但不溶opaf，也通过pafr独立的机制。小鼠嗜酸性粒细胞在对PAF或lysoPAF的反应中不释放细胞因子，但在对IL-6的反应中能够释放细胞因子。总的来说，我们的工作提供了第一个直接证据，证明PAF在激活和诱导小鼠嗜酸性粒细胞脱颗粒中的作用，这是解释PAF介导的哮喘和过敏反应小鼠模型的关键特征。同样，我们记录并定义了不依赖于PAFR信号传导的PAF和lysoPAF介导的活性，这表明存在其他尚未被探索的分子信号通路，介导PAF、lysoPAF和密切相关的磷脂介质的反应。(250字)
Platelet activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a phospholipid mediator released from activated macrophages, mast cells, and basophils that promotes pathophysiologic inflammation. Eosinophil responses to PAF are complex and incompletely elucidated. We show here that PAF and its 2-deacetylated metabolite, lysoPAF, promote degranulation (release of eosinophil peroxidase), via a mechanism that is independent of the characterized PAF receptor (PAFR). Specifically, we demonstrate that receptor antagonists CV-3988 and WEB-2086, and pertussis toxin have no impact on PAF- or lysoPAF-mediated degranulation. Furthermore, cultured mouse eosinophils from PAFR−/− bone marrow progenitors degranulate in response to PAF and lysoPAF in a manner indistinguishable from their wild-type counterparts. In addition to PAF and lysoPAF, human eosinophils degranulate in response to lysophosphatidylcholine, but not phosphatidylcholine, lysophosphatidylethanolamine or phosphatidylethanolamine, demonstrating selective responses to phospholipids with a choline head-group and minimal substitution at the sn-2 hydroxyl. Human eosinophils release preformed cytokines in response to PAF, but not lysoPAF, also via a PAFR-independent mechanism. Mouse eosinophils do not release cytokines in response to PAF or lysoPAF, but are capable of doing so in response to IL-6. Overall, our work provides the first direct evidence for a role for PAF in activating and inducing degranulation of mouse eosinophils, a crucial feature for the interpretation of mouse models of PAF-mediated asthma and anaphylaxis. Likewise, we document and define PAF and lysoPAF-mediated activities that are not dependent on signaling via PAFR, suggesting the existence of other, as yet to be explored, molecular signaling pathways mediating responses from PAF, lysoPAF and closely-related phospholipid mediators. [250 words]
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影响因子：
16.6
作者：
HANAHAN, DJ
通讯作者：
HANAHAN, DJ
影响因子：
2.2
作者：
Adamko, DJ;Wu, YQ;Moqbel, R
通讯作者：
Moqbel, R
影响因子：
2.8
作者：
Kato, M;Kita, H;Kimura, H
通讯作者：
Kimura, H
在缺乏血小板激活因子受体的小鼠中，对内毒素具有完整敏感性的过敏反应受损。
影响因子：
15.3
作者：
Ishii, S;Kuwaki, T;Nagase, T;Maki, K;Tashiro, F;Sunaga, S;Cao, W H;Kume, K;Fukuchi, Y;Ikuta, K;Miyazaki, J;Kumada, M;Shimizu, T
通讯作者：
Shimizu, T
影响因子：
5.1
作者：
Kasperska-Zajac, A.;Brzoza, Z.;Rogala, B.
通讯作者：
Rogala, B.