Hellewell P G, Henson P M, Downey G P, Worthen G S
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver 80206.
J Appl Physiol (1985). 1991 Mar;70(3):1184-93. doi: 10.1152/jappl.1991.70.3.1184.
The intrapulmonary instillation of C5a results in a local inflammatory response that, in this site, is accompanied by a decrease in local blood flow. Reversal of this decrease by vasodilators or the thromboxane synthesis inhibitor dazmegral has been shown to result in enhanced lung inflammation. In the present study the mechanisms underlying the decrease in flow in pulmonary inflammation were investigated in the rabbit in vivo and in the isolated blood-perfused rabbit lung. In vivo, the decrease in local blood flow was shown to be dependent on circulating neutrophils. In the isolated blood-perfused lung, inflammation induced by airway instillation of C5a was similar histologically to that seen in vivo and was also accompanied by a decrease in local blood flow. The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989. Furthermore, no decrease occurred in aspirin-treated lungs perfused with normal blood, suggesting that the source of thromboxane was lung rather than circulating cells. The decrease in blood flow in inflammation did not appear to be a consequence of hypoxic vasoconstriction. Inflammation in the guinea pig lung was also accompanied by a decrease in local blood flow and was also prevented by dazmegral and PAF antagonists. We conclude that local inflammation in the lung is accompanied by a decrease in blood flow that involves neutrophils and the lipid mediators PAF and thromboxane. We suggest that this form of negative feedback by the neutrophil serves to control the inflammatory response.
向肺内注入C5a会引发局部炎症反应,在此部位,炎症会伴随局部血流减少。血管扩张剂或血栓素合成抑制剂达美格雷可逆转这种血流减少,结果显示会加剧肺部炎症。在本研究中,我们在兔体内以及离体血液灌注的兔肺中研究了肺部炎症中血流减少的潜在机制。在体内,局部血流减少被证明依赖于循环中的中性粒细胞。在离体血液灌注肺中,气道注入C5a诱导的炎症在组织学上与体内所见相似,且同样伴随局部血流减少。血流减少似乎需要循环中的中性粒细胞,达美格雷以及血小板活化因子(PAF)拮抗剂WEB 2086和L-659,989可预防这种情况。此外,用正常血液灌注的阿司匹林处理的肺中未出现血流减少,这表明血栓素的来源是肺而非循环细胞。炎症中血流减少似乎不是缺氧性血管收缩的结果。豚鼠肺中的炎症也伴随局部血流减少,达美格雷和PAF拮抗剂也可预防这种情况。我们得出结论,肺部局部炎症伴随血流减少,这涉及中性粒细胞以及脂质介质PAF和血栓素。我们认为中性粒细胞的这种负反馈形式有助于控制炎症反应。