脂多糖
支气管肺泡灌洗
脂磷壁酸
酵母多糖
肿瘤坏死因子α
免疫学
趋化因子
生理盐水
药理学
医学
中性粒细胞
CD18型
化学
炎症
肺
生物
内科学
金黄色葡萄球菌
流式细胞术
体外
整合素αM
生物化学
细菌
遗传学
作者
James G. Wagner,Kevin E. Driscoll,Robert A. Roth
标识
DOI:10.1165/ajrcmb.20.4.3481
摘要
In rat models of Gram-negative pneumonia, pulmonary emigration of neutrophils (polymorphonuclear leukocytes [PMNs]) is blocked when rats are made endotoxemic by an intravenous administration of endotoxin (lipopolysaccharide [LPS]). To test whether dysfunctional PMN migratory responses in the endotoxemic rat are specific for airway endotoxin, we gave rats intrapulmonary stimuli known to elicit different adhesion pathways for pulmonary PMN migration. Sprague-Dawley rats were treated intravenously with either saline or LPS and then instilled intratracheally with either sterile saline, LPS from Escherichia coli, interleukin (IL)-1, hydrochloric acid (HCl), zymosan-activated serum (ZAS), or lipoteichoic acid (LTA). Three hours later, accumulation of PMNs and protein in bronchoalveolar lavage fluid (BALF) were assessed. BALF PMN accumulation in response to intratracheal treatment with LPS (100%), IL-1 (100%), ZAS (40%), and LTA (58%) was inhibited by endotoxemia. In rats given intratracheal HCl, BALF PMN numbers were unaffected by intravenous LPS. The pattern of inhibition of migration suggests that intravenous LPS only inhibits migration in response to stimuli for which migration is CD18-dependent. In contrast to PMN migration, BALF protein accumulation was inhibited by intravenous LPS only when IL-1 or LPS was used as the intratracheal stimulus. To characterize further the differential responses to the various airway stimuli, the appearance in BALF of tumor necrosis factor-alpha (TNF-alpha) and the PMN chemokine macrophage inflammatory protein (MIP)-2 was measured. Accumulation of PMNs in BALF correlated with the BALF concentrations of MIP-2 (r = 0.846, P < 0.05) and TNF (r = 0.911; P < 0.05). The ability of intravenous LPS to inhibit pulmonary PMN migration correlated weakly with MIP-2 (r = 0.659; P < 0.05) and with TNF (r = 0.413; P > 0.05) concentrations in BALF. However, this correlation was strengthened for TNF (r = 0.752; P < 0.05) when data from IL-1-treated animals were excluded. Thus, the presence in BALF of inflammatory mediators that are known to promote CD18-mediated migration correlates with endotoxemia-related inhibition of PMN migration. Furthermore, the pattern of inhibition of pulmonary PMN migration during endotoxemia is consistent with the CD18 requirement of each migratory stimulus.
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