Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites.
Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites.
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DOI：
10.1172/jci110548
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发表时间：
1982-05
期刊：
影响因子：
--
通讯作者：
G. Till;K. Johnson;R. Kunkel;P. Ward
中科院分区：
文献类型：
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作者：
G. Till;K. Johnson;R. Kunkel;P. Ward
眼镜蛇毒因子对补体系统的血管内激活会导致急性肺损伤，这可以通过肺血管通透性的增加来定量。缺乏磷脂酶 A2 活性的眼镜蛇毒因子制剂保留了完整的肺损伤能力。肺损伤与血清中先前出现的趋化活性有关，同时出现严重的中性粒细胞减少症。趋化活性在免疫化学上与人 C5a 相关。形态学研究揭示了肺泡毛细血管内皮细胞衬里的不连续性、这些区域内皮细胞的损伤和/或破坏、与血管基底膜直接接触的中性粒细胞堵塞肺毛细血管、肺泡腔和邻近受损内皮细胞的区域中存在纤维蛋白以及肺泡内出血。在先前已耗尽中性粒细胞的动物中，肺损伤显着减轻。静脉注射超氧化物歧化酶或过氧化氢酶也能提供显着的保护，防止肺部损伤。对肺部损伤的保护作用很小。用抗组胺药对大鼠进行预处理所提供的保护作用非常小。这些研究表明，血管内补体系统的激活导致中性粒细胞聚集和激活、中性粒细胞肺内毛细血管隔离和血管损伤，这可能与补体激活的中性粒细胞产生有毒氧代谢物有关。
Intravascular activation of the complement system with cobra venom factor results in acute lung injury, which has been quantitated by increases in lung vascular permeability. Cobra venom factor preparations devoid of phospholipase A2 activity retain full lung-damaging capacity. The lung injury is associated with the preceding appearance of chemotactic activity in the serum coincident with the development of a profound neutropenia. The chemotactic activity is immunochemically related to human C5a. Morphologic studies have revealed discontinuities in the endothelial cell lining of lung alveolar capillaries, damage and/or destruction of endothelial cells in these areas, plugging of pulmonary capillaries with neutrophils that are in direct contact with vascular basement membrane, the presence of fibrin in alveolar spaces and in areas adjacent to damaged endothelial cells, and intraalveolar hemorrhage. Lung injury is dramatically attenuated in animals that have been previously neutrophil depleted. Teh intravenous injection of superoxide dismutase or catalase also provides significant protection from the pulmonary damage. Very little protection from the pulmonary damage. Very little protection is afforded by pretreatment of rats with antihistamine. These studies suggest that intravascular activation of the complement system leads to neutrophil aggregation and activation, intrapulmonary capillary sequestration of neutrophils, and vascular injury, which may be related to production of toxic oxygen metabolites by complement-activated neutrophils.