Farber H W, Kozlova M, Moldobalva A, Charles A, Danilov S M
Pulmonary Center, Boston University School of Medicine, MA 02118.
Tissue Cell. 1992;24(3):355-66. doi: 10.1016/0040-8166(92)90052-9.
Previous studies have demonstrated that the interaction of cultured bovine aortic and pulmonary arterial endothelial cells and the proinflammatory vasoactive amines histamine, serotonin, and angiotensin II, causes production of three novel lipid neutrophil-specific chemoattractants that are distinct from other phospholipid or lipid neutrophil chemoattractants. In this study, we investigated the species and site specificity of this inflammatory response by incubating human aortic and pulmonary arterial endothelial cells with histamine, serotonin, and angiotensin II and assaying the supernatants for their effect on neutrophil migration. Each of these vasoactive amines caused production of neutrophil chemoattractant activity in a concentration dependent manner in both cell types. For each amine, production was blocked by a specific antagonist: cimetidine for histamine, methiothepin for serotonin-stimulated aortas, ketanserin for serotonin-stimulated pulmonary arteries, and saralasin for angiotensin II. In each case, all chemoattractant activity partitioned into the organic phase and resolution by HPLC yielded two chemotactic lipids. As with the lipid chemoattractants produced by bovine endothelial cells, these lipids did not coelute with PAF, LTB4, 5-HETE, or 15-HETE, nor did they increase lymphocyte or monocyte migration. The pattern of chemotactic activity following resolution by HPLC was similar in both human aortic and pulmonary arterial endothelial cells, but was different from that of bovine aortic and pulmonary arterial endothelial cells in that only two chemoattractant lipids appeared; the third chemotactic lipid was never produced. These studies demonstrate that human endothelial cells may actively participate in neutrophil enriched local inflammatory responses by production of neutrophil-specific chemotactic factors. They also suggest this response may be dissimilar depending on the site and species from which the endothelial cells originate.
先前的研究表明，培养的牛主动脉和肺动脉内皮细胞与促炎血管活性胺组胺、5-羟色胺和血管紧张素II相互作用，会产生三种新型脂质中性粒细胞特异性趋化因子，这些趋化因子不同于其他磷脂或脂质中性粒细胞趋化因子。在本研究中，我们通过将人主动脉和肺动脉内皮细胞与组胺、5-羟色胺和血管紧张素II孵育，并检测上清液对中性粒细胞迁移的影响，来研究这种炎症反应的物种和部位特异性。这些血管活性胺中的每一种都以浓度依赖性方式在两种细胞类型中引起中性粒细胞趋化活性的产生。对于每种胺，其产生均被特异性拮抗剂阻断：组胺用西咪替丁，5-羟色胺刺激的主动脉用甲硫噻平，5-羟色胺刺激的肺动脉用酮色林，血管紧张素II用沙拉新。在每种情况下，所有趋化活性都分配到有机相中，通过高效液相色谱法分离得到两种趋化脂质。与牛内皮细胞产生的脂质趋化因子一样，这些脂质与血小板活化因子、白三烯B4、5-羟基二十碳四烯酸或15-羟基二十碳四烯酸不共洗脱，也不会增加淋巴细胞或单核细胞的迁移。在人主动脉和肺动脉内皮细胞中，高效液相色谱法分离后的趋化活性模式相似，但与牛主动脉和肺动脉内皮细胞不同，因为只出现了两种趋化脂质；从未产生第三种趋化脂质。这些研究表明，人内皮细胞可能通过产生中性粒细胞特异性趋化因子而积极参与富含中性粒细胞的局部炎症反应。它们还表明，这种反应可能因内皮细胞来源的部位和物种而异。
