THE ROLE OF NEUTROPHILS, OXIDANTS, AND PROTEASES IN THE PATHOGENESIS OF ACID PULMONARY INJURY
THE ROLE OF NEUTROPHILS, OXIDANTS, AND PROTEASES IN THE PATHOGENESIS OF ACID PULMONARY INJURY
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DOI：
10.1097/00000542-199210000-00023
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发表时间：
1992-10-01
期刊：
影响因子：
8.8
通讯作者：
JOHNSON, KJ
中科院分区：
文献类型：
--
作者：
KNIGHT, PR;DRUSKOVICH, G;JOHNSON, KJ
我们最近报道了一种大鼠非致死性酸吸入肺炎的双相损伤模式。第一阶段包括直接组织损伤的直接影响，第二阶段与中性粒细胞炎症反应有关。利用这一模型，本报告研究了中性粒细胞、氧化剂和蛋白水解酶在肺损伤第二阶段的发病机制中的可能作用。大鼠气管内滴入pH=1.25的生理盐水/盐酸造成酸吸入损伤。通过测量肺泡毛细血管对I-125标记白蛋白的通透性程度(通透性指数[PI])来评价肺损伤。多克隆抗中性粒细胞抗体致中性粒细胞减少的大鼠吸酸后6h的PI(0.44+/-0.07，P<；0.05)低于中性粒细胞计数正常的同类损伤大鼠(PI=0.85+/-0.03)。在该模型中，尽管中性粒细胞似乎对肺损伤的充分发展是必需的，但静脉和/或气管内给予不同浓度的去铁胺或过氧化氢酶对损伤没有保护作用。这表明中性粒细胞氧化剂在损伤中的作用最小。伤后6h，生理盐水/盐酸(pH=1.25)处理组大鼠肺泡灌洗液中无白细胞丝氨酸蛋白酶活性(1,477+/-438u/ml，P<；0.05)显著高于生理盐水/盐酸(pH=5.3)对照组(2.7+/-0.2u/ml)。这项研究支持这样的假设，即中性粒细胞是酸诱导的肺损伤充分表达所必需的，白细胞衍生氧化剂的产生似乎不是这种损伤的主要机制。事实上，在支气管肺泡灌洗液中存在高水平的丝氨酸蛋白酶是这些酶在这种损伤中发挥重要作用的强有力的推定证据。这项研究的结果表明，新的治疗策略的可能性旨在减少这种潜在的致命并发症造成的肺损伤。
We recently reported a biphasic injury pattern of nonlethal acid aspiration pneumonitis in rats. The first phase consisted of the immediate effects of the direct tissue injury, and the second phase was associated with a neutrophilic inflammatory response. Using this model, the present report examines the possible role of neutrophils, oxidants, and proteases in the pathogenesis of the second phase of this lung injury. Acid aspiration injury was induced by instillation of saline/HCl, pH = 1.25, into the trachea of rats. Lung injury was assessed by measuring the degree of alveolar capillary permeability to I-125-labeled albumin (permeability index [PI]). Rats made neutropenic with polyclonal antineutrophil antibody had a lower PI (0.44 +/- 0.07, P < 0.05) 6 h after acid aspiration than similarly injured animals with normal whole blood neutrophil counts (PI = 0.85 +/- 0.03). Even though neutrophils appeared necessary for the full development of the lung injury in this model, the administration of different intravenous and/or intratracheal concentrations of either deferoxamine or catalase offered no protection against injury. This suggests that neutrophil oxidants were minimally involved in the injury. Large increases in leukocyte-free serine protease activity (1,477 +/- 438 u/ml, P < 0.05) were detected in the bronchoalveolar lavage fluid from the saline/HCI, pH = 1.25, injured rats at 6 h postinjury, as compared to saline/HCI, pH = 5.3, treated control animals (2.7 +/- 0.2 u/ml). This study supports the hypothesis that neutrophils are necessary for the full expression of acid-induced lung injury and that the generation of leukocyte-derived oxidants does not appear to be the primary mechanism involved in this injury. Indeed, the presence of high levels of serine proteases in the bronchoalveolar lavage fluid is strong presumptive evidence that these enzymes play an important role in this injury. Results from this study suggest the possibility of new treatment strategies aimed at decreasing the lung injury from this potentially lethal complication.