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血小板活化因子受体在大鼠胰腺微血管内皮细胞中的定位。

Localization of the platelet-activating factor receptor to rat pancreatic microvascular endothelial cells.

作者信息

Flickinger B D, Olson M S

机构信息

Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas, USA.

出版信息

Am J Pathol. 1999 May;154(5):1353-8. doi: 10.1016/S0002-9440(10)65389-8.

Abstract

Platelet-activating factor (PAF) is a potent lipid autocoid involved in numerous inflammatory processes. Although PAF plays a key role as a mediator of inflammation in acute pancreatitis, the site(s) of action of PAF in the pancreas remains unknown. One of the aims of this study was to identify cell types within the pancreas expressing the PAF receptor using immunohistochemical protocols. Additionally, pancreatic microvascular endothelial cells were isolated and examined for the PAF receptor using immunohistochemistry, reverse transcription-polymerase chain reaction, and intracellular calcium responses to PAF exposure. Immunohistochemical analysis of pancreatic slices using an antibody directed toward the N-terminus of the PAF receptor revealed specific localization to the vascular endothelium with no localization to other pancreatic cell types. Reverse transcription-polymerase chain reaction of RNA isolated from cultured pancreatic islet endothelial cells yielded the predicted amplicon for the PAF receptor. Cultured pancreatic islet endothelial cells responded to PAF as measured by a transient increase in intracellular calcium, which was ameliorated in the presence of a PAF receptor antagonist. The results demonstrate the localization of PAF receptors on the pancreatic vascular endothelium. The presence of PAF receptors on the pancreatic vascular endothelium provides a defined, highly localized target for therapeutic intervention.

摘要

血小板活化因子(PAF)是一种强效脂质自分泌物质,参与众多炎症过程。尽管PAF在急性胰腺炎中作为炎症介质发挥关键作用,但其在胰腺中的作用位点仍不清楚。本研究的目的之一是使用免疫组织化学方法鉴定胰腺内表达PAF受体的细胞类型。此外,分离胰腺微血管内皮细胞,并用免疫组织化学、逆转录-聚合酶链反应以及检测PAF刺激后的细胞内钙反应等方法检测PAF受体。使用针对PAF受体N端的抗体对胰腺切片进行免疫组织化学分析,结果显示PAF受体特异性定位于血管内皮,而在其他胰腺细胞类型中无定位。从培养的胰岛内皮细胞中分离的RNA进行逆转录-聚合酶链反应,得到了PAF受体的预期扩增子。培养的胰岛内皮细胞对PAF有反应,表现为细胞内钙短暂增加,而在PAF受体拮抗剂存在时这种增加有所改善。结果表明PAF受体定位于胰腺血管内皮。胰腺血管内皮上PAF受体的存在为治疗干预提供了一个明确的、高度局限的靶点。

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Lexipafant (BB-882), a potent PAF antagonist in acute pancreatitis.
Adv Exp Med Biol. 1996;416:361-3. doi: 10.1007/978-1-4899-0179-8_58.
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