Issekutz A C, Szpejda M
Lab Invest. 1986 Mar;54(3):275-81.
Platelet activating factor (PAF) has many proinflammatory properties. It is a polymorphonuclear leukocyte chemotactic factor, it aggregates platelets, increases vascular permeability, and is generated by inflammatory cells. To determine the possible in vivo role of PAF in inflammation, we examined the effects of the PAF antagonist and structural analogue, CV3988 on acute inflammatory responses in the skin of rabbits. Initial experiments indicated that CV3988 (10 mg/kg) was a specific inhibitor of PAF responses in vivo since it abolished neutropenia and thrombocytopenia induced by intravenous (iv) PAF infusion without effecting the response to f-met-leu-phe. In dermal inflammation, 125I-albumin, 111In-labeled platelets, 51Cr-labeled leukocytes, and 86RbCl were used to simultaneously quantitate protein exudation, platelet deposition, leukocyte accumulation, and blood flow in the lesions. CV3988 inhibited inflammatory responses to intradermal injection of PAF by 65 to 85% but it did not inhibit thrombin-induced platelet deposition or bradykinin and histamine-induced protein exudation. CV3988 treatment inhibited by 60 to 80% (p less than 0.01) the platelet deposition occurring at the peak of the reaction (1 1/2 hours) induced by the intradermal injection of zymosan, zymosan activated plasma, endotoxin, and the reversed passive Arthus reaction. Protein exudation was inhibited by 67 to 85% (p less than 0.1) and leukocyte accumulation was inhibited by 24 to 35% (p less than 0.05), but only in the zymosan and reversed passive Arthus reactions, respectively. Inflammatory hyperemia (increases blood flow) was not affected by CV3988 treatment. We conclude that in certain inflammatory reactions, PAF may mediate platelet deposition and protein exudation. The marginal effect of CV3988 on leukocyte accumulation suggests that the leukotactic activity of PAF is relatively less important in vivo.
血小板活化因子（PAF）具有多种促炎特性。它是一种多形核白细胞趋化因子，能使血小板聚集，增加血管通透性，由炎症细胞产生。为了确定PAF在炎症中可能的体内作用，我们研究了PAF拮抗剂及结构类似物CV3988对兔皮肤急性炎症反应的影响。初步实验表明，CV3988（10毫克/千克）是体内PAF反应的特异性抑制剂，因为它消除了静脉注射PAF引起的中性粒细胞减少和血小板减少，而不影响对f-甲硫-亮-苯丙氨酸的反应。在皮肤炎症中，使用125I-白蛋白、111In标记的血小板、51Cr标记的白细胞和86RbCl同时定量病变部位的蛋白质渗出、血小板沉积、白细胞聚集和血流。CV3988抑制皮内注射PAF引起的炎症反应达65%至85%，但不抑制凝血酶诱导的血小板沉积或缓激肽和组胺诱导的蛋白质渗出。CV3988治疗抑制皮内注射酵母聚糖、酵母聚糖激活血浆、内毒素和反向被动Arthus反应诱导的反应峰值（1.5小时）时出现的血小板沉积达60%至80%（p小于0.01）。蛋白质渗出抑制了67%至85%（p小于0.1），白细胞聚集抑制了24%至35%（p小于0.05），但分别仅在酵母聚糖和反向被动Arthus反应中出现。炎症性充血（血流量增加）不受CV3988治疗的影响。我们得出结论，在某些炎症反应中，PAF可能介导血小板沉积和蛋白质渗出。CV3988对白细胞聚集的边缘效应表明，PAF的趋化活性在体内相对不太重要。
