Ramos B F, Zhang Y, Jakschik B A
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
Eur J Immunol. 1992 Sep;22(9):2381-5. doi: 10.1002/eji.1830220930.
The activation of the clotting system is an important process during inflammation to contain the injury and initiate tissue repair. In the present study, we investigated the effect of mast cells on fibrin deposition in reverse passive Arthus reaction in mast cell-deficient WBB6F1-W/Wv(W/Wv) and control WBB6F1-(+)/+(+/+) mice, that were given 125I-labeled fibrogen intravenousty. An antibody dose-dependent increase in radioactivity was observed in the challenged skin sites. Sequential water and urea extractions characterized the radioiodinated fibrinogen derivatives present in the tissue. The radioactivity found in the various fractions of the stimulated samples from +/+ was 2-10-fold higher than that in specimens from W/Wv mice. The greatest difference was observed in the urea-insoluble pellet (cross-linked fibrin and its early degradation products). Reconstitution of W/Wv mice with mast cells augmented the response to levels similar to those in +/+ mice. Pretreatment with the antihistamine pyrilamine blocked the accumulation of 125I-labeled fibrinogen and its derivatives by approximately 70% in +/+ but not in W/Wv mice. Inhibition of leukotriene synthesis by A-63162 markedly decreased the accumulation of iodinated fibrinogen in both +/+ and W/Wv mice. The data suggest that mast cells and their vasoactive mediator histamine contribute to the exudation of clotting factors, which results in fibrin deposition and that mast cells also enhance fibrin cross-linkage.
凝血系统的激活是炎症过程中的一个重要环节，有助于控制损伤并启动组织修复。在本研究中，我们研究了肥大细胞对肥大细胞缺陷型WBB6F1-W/Wv（W/Wv）小鼠和对照WBB6F1-（+）/ +（+/ +）小鼠反向被动Arthus反应中纤维蛋白沉积的影响，这些小鼠通过静脉注射给予125I标记的纤维蛋白原。在受攻击的皮肤部位观察到抗体剂量依赖性的放射性增加。通过连续的水和尿素提取对组织中存在的放射性碘化纤维蛋白原衍生物进行了表征。来自+/ +的刺激样品各部分中的放射性比来自W/Wv小鼠的标本中的放射性高2-10倍。在尿素不溶性沉淀（交联纤维蛋白及其早期降解产物）中观察到最大差异。用肥大细胞重建W/Wv小鼠可增强反应，使其水平与+/ +小鼠相似。用抗组胺药吡苄明预处理可使+/ +小鼠中125I标记的纤维蛋白原及其衍生物的积累减少约70%，但对W/Wv小鼠无效。A-63162抑制白三烯合成可显著降低+/ +和W/Wv小鼠中碘化纤维蛋白原的积累。数据表明，肥大细胞及其血管活性介质组胺有助于凝血因子的渗出，从而导致纤维蛋白沉积，并且肥大细胞还可增强纤维蛋白交联。
