CD18 adhesion receptors, tumor necrosis factor, and neutropenia during septic lung injury.
CD18 adhesion receptors, tumor necrosis factor, and neutropenia during septic lung injury.
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脓毒性肺损伤期间的 CD18 粘附受体、肿瘤坏死因子和中性粒细胞减少症。
DOI：
10.1016/0022-4804(91)90198-u
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Sugerman,HJ
中科院分区：
文献类型：
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作者：
Walsh,CJ;Leeper-Woodford,SK;Carey,PD;Cook,DJ;Bechard,DE;Fowler,AA;Sugerman,HJ
肺微血管中中性粒细胞（PMN）的隔离和相关的中性粒细胞减少症是脓毒性肺损伤实验模型的特征。脓毒性肺损伤期间中性粒细胞动力学改变的病因尚不清楚，但可能部分是由于活化的中性粒细胞与肺内皮的粘附性增加所致。本研究探讨了猪脓毒性肺损伤模型中 PMN CD18 粘附受体的表达、中性粒细胞减少症的演变以及血浆肿瘤坏死因子 (TNF) 活性之间的关系。通过输注活铜绿假单胞菌（5×108CFU/ml，0.3ml/20kg/min）60分钟诱导急性肺损伤（Ps组，n=6）。对照动物（C 组，n= 3）接受 60 分钟的无菌 0.9% 盐水输注。通过定量免疫荧光流式细胞术测量循环 PMN 的 CD18 表达。通过L929成纤维细胞溶细胞测定法测量血浆TNF活性。 P 组在 30 分钟时出现显着的中性粒细胞减少症（基线时为 14.9 ± 2.5 vs 23.4 ± 3.3 × 103 细胞/μl，P < 0.05，方差分析），循环中性粒细胞在 60 分钟时表现出 CD18 表达显着增加（6.34 ± 0.72 vs 5.01 ± 0.52 等效可溶性荧光分子 (ESFM) × 103 基线，P < 0.05，方差分析）。 P 组的血浆 TNF 活性在 30 分钟内显着增加（基线时为 2.5 ± 0.9 vs 0.7 ± 0.3 U/ml）。 C 组中 PMN 计数、PMN CD18 表达或血浆 TNF 活性没有显着变化。在体外互补研究中，用重组人 TNF-α (n = 5) 刺激的猪 PMN 显示 CD18 表达呈时间和剂量依赖性增加。我们认为，该模型中的中性粒细胞减少症部分是通过 CD18 依赖性机制发生的，并且 TNF 有可能介导该过程。
Sequestration of neutrophils (PMNs) in the pulmonary microvasculature and associated neutropenia are characteristic features of experimental models of septic lung injury. The etiology of altered PMN kinetics during septic lung injury is uncertain, but may be partially due to increased adhesiveness of activated PMNs to pulmonary endothelium. This study examines the relationship between the expression of PMN CD18 adhesion receptors, the evolving neutropenia, and plasma tumor necrosis factor (TNF) activity in a porcine model of septic lung injury. Acute lung injury was induced by infusion of livePseudomonas aeruginosa(5 × 108CFU/ml at 0.3 ml/20 kg/min) for 60 min (Group Ps,n= 6). Control animals (Group C,n= 3) received a 60-min infusion of sterile 0.9% saline. CD18 expression of circulating PMNs was measured by quantitative immunofluorescent flow cytometry. Plasma TNF activity was measured by L929 fibroblast cytolytic assay. Group Ps developed a significant neutropenia by 30 min (14.9 ± 2.5 vs 23.4 ± 3.3 × 103cells/μl at baseline,P< 0.05, ANOVA) with circulating neutrophils exhibiting significantly increased CD18 expression by 60 min (6.34 ± 0.72 vs 5.01 ± 0.52 equivalent soluble fluorescence molecules (ESFM) × 103at baseline,P< 0.05, ANOVA). Group Ps demonstrated a significant increase in plasma TNF activity by 30 min (2.5 ± 0.9 vs 0.7 ± 0.3 U/ml at baseline). There was no significant change in PMN count, PMN CD18 expression, or plasma TNF activity in Group C. In complimentaryin vitrostudies, porcine PMNs stimulated with recombinant human TNF-α (n= 5) demonstrated a time- and dose-dependent increase in CD18 expression. We suggest that neutropenia in this model occurs in part by a CD18-dependent mechanism and that TNF has the potential to mediate the process.