ROLE OF COMPLEMENT AND INFLAMMATORY CELLS IN LUNG INJURY

补体（C5）衍生的肽已经被认为是 急性肺损伤（即成人呼吸窘迫综合征，ARDS）， 由于它们能够引起多形核的螯合， 白细胞（PMN）在肺血管和随后的损害， 内皮细胞 无论是负责C5衍生的确切身份， 肽也没有PMN介导的损伤的机制尚未确定。 拟议研究的目的是检验假设， 血小板衍生因子和/或花生四烯酸的代谢物 C5 a和/或C5 a des Arg刺激的PMN改变了 肺微血管内皮细胞 拟议的研究将 涉及兔C5 a和C5 a des Arg纯化和表征 以及旨在研究兔子和老鼠之间相互作用的实验 C5衍生肽、兔PMN和兔内皮细胞。 协同 肽刺激的PMN、前列腺素类和/或血小板因子之间的作用 增加血管通透性和PMN迁移到肺泡将是 在急性肺损伤的动物模型中评估。 自然的作用 存在的调节蛋白（即羧肽酶N、共趋化因子和 趋化因子抑制剂）在调节这些相互作用中的作用， 在动物模型和体外测定。 这些研究的结果 应提供有关补体相互作用的新信息 系统、中性粒细胞、血小板和血管内皮在发病中的作用 的ARDS。 这些研究的结果也应该提供线索， 探讨合理的防治措施。

Complement (C5)-derived peptides have been implicated as being mediators of acute lung injury (i.e. adult respiratory distress syndrome, ARDS), by virtue of their ability to cause sequestration of polymorphonuclear leukocytes (PMN) in the pulmonary vasculature and subsequent damage to endothelium. Neither the precise identity of the responsible C5-derived peptide nor the mechanism of PMN-mediated injury has yet been determined. The objective of the proposed research is to test the hypothesis that platelet-derived factors and/or metabolites of arachidonic acid together with C5a- and/or C5a des Arg-stimulated PMN alter the integrity of pulmonary microvascular endothelial cells. The proposed studies will involve purification and characterization of rabbit C5a and C5a des Arg as well as experiments designed to examine interaction between rabbit C5-derived peptides, rabbit PMN and rabbit endothelial cells. Synergistic effects betwee peptide-stimulated PMN, prostanoids and/or platelet factors on increased vascular permeability and PMN emigration into alveoli will be assessed in animal models of acute lung injury. The role of naturally occurring regulatory proteins (i.e. carboxypeptidase N, cochemotaxin, and chemotactic factor inhibitor) in modulating these interactions will also be determined in animal models and in vitro. Results from these studies should provide new information concerning interaction of the complement system, neutrophils, platelets and vascular endothelium in the pathogenesis of ARDS. Results of these studies should also provide clues to the rational investigation of prophylactic and therapeutic measures for ARDS.