Merck
  • 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.

Journal of immunology (Baltimore, Md. : 1950) (2010-04-28)
Kimberly D Dyer, Caroline M Percopo, Zhihui Xie, Zhao Yang, John Dongil Kim, Francis Davoine, Paige Lacy, Kirk M Druey, Redwan Moqbel, Helene F Rosenberg
要旨

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 in this article that PAF and its 2-deacetylated metabolite (lysoPAF) promote degranulation (release of eosinophil peroxidase) via a mechanism that is independent of the characterized 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 they 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 unexplored molecular signaling pathways mediating responses from PAF, lysoPAF, and closely related phospholipid mediators.

材料
製品番号
ブランド
製品内容

Avanti
16:0 PC(DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, powder
Avanti
16:0 PC(DPPC), Avanti Polar Lipids
Avanti
16:0 リゾPC, Avanti Polar Lipids
Avanti
16:0 PE, Avanti Polar Lipids
Sigma-Aldrich
β-アセチル-γ-O-ヘキサデシル-L-α-ホスファチジルコリン, ≥98%
Avanti
16:0リゾPE, Avanti Polar Lipids, powder
Sigma-Aldrich
WEB2086, ≥98% (HPLC)
Avanti
16:0 Lyso PC, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine, chloroform
Sigma-Aldrich
1-O-パルミチル-sn-グリセロ-3-ホスホコリン, ≥99%, synthetic
Avanti
C18 Lyso PAF, Avanti Polar Lipids 878120P, powder