The expression and localization of plasma platelet-activating factor acetylhydrolase in endotoxemic rats
The expression and localization of plasma platelet-activating factor acetylhydrolase in endotoxemic rats
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DOI：
10.1074/jbc.m001462200
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发表时间：
2000-06-30
影响因子：
4.8
通讯作者：
Olson, MS
中科院分区：
文献类型：
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作者：
Howard, KM;Olson, MS
血小板活化因子（PAF）和PAF样磷脂的产生也与PAF受体结合，涉及许多病理情况，包括细菌内毒素血症和损伤性氧化损伤。PAF和PAF样磷脂被PAF乙酰水解酶水解并失活。在完整的大鼠中，将脂多糖（LPS）输注到肠系膜静脉中作为急性肝脏内毒素血症模型。我们确定肝脏对LPS暴露的反应是产生血浆型PAF乙酰水解酶mRNA和蛋白质表达，特别是在肝脏的巨噬细胞中。用免疫组织化学方法定义的抗ED1抗体在盐水处理动物肝脏中的肝巨噬细胞不含可检测到的PAF乙酰水解酶，在体内LPS处理24小时后，免疫组织化学检测到ED1染色细胞数量轻微增加，ED1阳性细胞现在含有丰富的PAF乙酰水解酶。全身给药LPS导致PAF乙酰水解酶在一些组织中的表达增加。在所检测的组织中，PAF乙酰水解酶的表达在肺中增加最多，其次是脾脏、肝脏、肾脏和胸腺。此外，循环白细胞和腹腔巨噬细胞中PAF乙酰水解酶mRNA的表达在全身暴露于LPS的情况下增加。我们检测了PAF乙酰水解酶表达的调节，并证明了PAF受体拮抗剂BN 50739和WEB 2170的管理。血浆型PAF乙酰水解酶表达的上调是提高局部和全身灭活PAF和氧化磷脂的能力的重要机制，从而减少内毒素暴露引起的PAF介导的病理生理。肝小叶中PAF乙酰水解酶的丰富可能限制了由PAF合成引起的内毒素介导的组织损伤。
The production of platelet-activating factor (PAF) and PAF-like phospholipids that also bind the PAF receptor are implicated in numerous pathological situations including bacterial endotoxemia and injury-induced oxidative damage. PAF and PAF-like phospholipids are hydrolyzed and inactivated by the enzyme PAF acetylhydrolase, In the intact rat, infusion of lipopolysaccharide (LPS) into a mesenteric vein served as an acute, liver-focused model of endotoxemia. We determined that the liver responds to LPS exposure with the production of plasma-type PAF acetylhydrolase mRNA and protein expression specifically in the resident macrophages of the liver. Liver macrophages, defined immunohistochemically using antibodies against ED1, present in livers from saline-treated animals contained no detectable PAF acetylhydrolase, Twenty-four hours following in vivo LPS administration, immunohistochemistry detected a slight increase in the number of ED1 staining cells and the ED1-positive cells now contained an abundance of PAF acetylhydrolase. The systemic administration of LPS resulted in increased expression of PAF acetylhydrolase in several tissues. Of the tissues examined, the greatest increase in PAF acetylhydrolase expression was observed in lung followed by increases in spleen, liver, kidney, and thymus, Additionally, the expression of PAF acetylhydrolase mRNA increased in circulating leukocytes and in peritoneal macrophages in response to systemic exposure to LPS, We examined the regulation of PAF acetylhydrolase expression and demonstrated the administration of the PAF receptor antagonists, BN 50739 and WEB 2170, inhibited by 50% the increase in PAF acetylhydrolase expression in response to LPS, The up-regulation of the plasma-type PAF acetylhydrolase expression constitutes an important mechanism for elevating the local and systemic ability to inactivate PAF and oxidized phospholipids in order to minimize PAF-mediated pathophysiology consequent from exposure to endotoxin, The abundance of PAF acetylhydrolase production in the liver lobule likely limits endotoxin-mediated tissue damage due to PAF synthesis.