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Expression of inflammatory cytokines and Fas in alveolar macrophages from ARDS patients

ARDS患者肺泡巨噬细胞炎症细胞因子和Fas的表达

基本信息

批准号：
10671438
负责人：
YAMASHITA Tomomitsu
金额：
$ 1.92万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671438/
关键词：
Acute lung injury Acute respiratory distress syndrome Alveolar macrophage Fas Cytokine ARDS

项目摘要

The objective of this study was to evaluate the role of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines together with apoptosis related factors in alveolar macrophages (AMs) in the pathogenesis of acute respiratory distress syndrome (ARDS) following sepsis. To investigate these expressions in AMs collected from ARDS patients following sepsis, the expression of iNOS and IL-1□,IL-6,IL-8 in AMs were determined by the immunofluorescent technique. The level of NOx, IL-1□,IL-6,and IL-8 in bronchoalveolar lavage fluid (BALF) supernatant and in serum were measured concurrently. To exclude the effect of the long-term ventilation, sepsis syndrome alone, and/or the administration of sedative drugs, all data obtained from patients with ARDS following sepsis were compared with the data from normal control subjects and from septic patients who had been mechanically ventilated for one week without fulfilling the criteria of ARDS (LTV group). Using immunofluorescent technique, our study identified the strong expression of iNOS in AMs of human lungs predominantly at the early stage of ARDS following sepsis. Whereas no expression of iNOS was observed in AMs from the control group, nor was observed in AMs from the LTV group. Another finding of this study is the marked increase of IL-6 and IL-8 levels in BALF supernatant and the serum from patients with ARDS as compared with the control and the LTV group. Also, statistically significant elevations were detected in NOx, IL-6 and IL-8 levels in BALF supernatant from the ARDS group compared with the control group. The result suggests that iNOS together with proinflammatory cytokines produced by AMs might play a pivotal role in the pathogenesis of acute lung injury and be useful for monitoring disorders in the lung of patients with ARDS following sepsis.

本研究旨在探讨诱导型一氧化氮合酶（iNOS）、促炎细胞因子和凋亡相关因子在脓毒症后急性呼吸窘迫综合征（ARDS）发病机制中的作用。为了研究脓毒症后急性呼吸窘迫综合征患者AM中这些表达，采用免疫荧光技术检测AM中iNOS和IL-1、IL-6、IL-8的表达。同时检测支气管肺泡灌洗液（BALF）上清液和血清中NOx、IL-1、IL-6和IL-8的水平。为了排除长期通气、脓毒症综合征和/或镇静药物给药的影响，将脓毒症后ARDS患者的所有数据与正常对照组和机械通气1周但不符合ARDS标准的脓毒症患者（LTV组）的数据进行比较。本研究应用免疫荧光技术检测了诱导型一氧化氮合酶在脓毒症后急性呼吸窘迫综合征（ARDS）早期肺泡巨噬细胞中的强表达。对照组AM中未见iNOS表达，LTV组AM中亦未见iNOS表达。本研究的另一个发现是，与对照组和LTV组相比，ARDS患者BALF上清液和血清中IL-6和IL-8水平显著升高。与对照组相比，ARDS组BALF上清液中NOx、IL-6和IL-8水平也显著升高。结果提示，诱导型一氧化氮合酶和AM产生的促炎细胞因子在脓毒症后急性肺损伤的发病机制中起重要作用，对监测脓毒症后ARDS患者的肺功能紊乱具有重要意义。