An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation .1. The roles of minor H antigens and endotoxin
An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation .1. The roles of minor H antigens and endotoxin
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DOI：
10.1182/blood.v88.8.3230.bloodjournal8883230
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发表时间：
1996-10-15
期刊：
影响因子：
20.3
通讯作者：
Ferrara, JLM
中科院分区：
文献类型：
--
作者：
Cooke, KR;Kobzik, L;Ferrara, JLM
特发性肺炎综合征（IPS）是指同种异体骨髓移植（BMT）后发生的弥漫性非感染性肺炎。我们使用特征良好的小鼠 BMT 系统 (B10.BR --> CBA) 开发了一种 IFS 模型，其中 BMT 后的肺损伤可以通过供体和宿主之间的微小组织相容性 (H) 抗原差异来诱导。在同基因和同种异体 BMT 前后对移植受者的肺部病理学和支气管肺泡灌洗 (BAL) 液进行分析。 BMT 后 2 周，未发现特定病理异常； 6 周时，仅在接受同种异体 BMT 的小鼠中观察到肺炎和血管和细支气管周围的单核细胞浸润，这种损伤与 BAL 液中内毒素（脂多糖 [LPS]）、中性粒细胞和肿瘤坏死因子 α 水平升高有关。从任何动物的呼吸道中均未分离出病理微生物。我们还测试了内毒素在这种损伤发生中的作用。移植后 6 周注射 LPS 仅对患有中度移植物抗宿主病的小鼠造成严重的肺损伤；观察到 BAL 中性粒细胞和肿瘤坏死因子 α 急剧增加，其中 12 只小鼠中有 4 只出现肺泡出血，但其他组没有出现这种情况。我们的结论是：（1）这种小鼠 BMT 系统是临床 IPS 的潜在有用模型； (2) 供体和受体之间微小的 H 差异可能是 IPS 发病机制的重要刺激因素； (3)BAL液中的内毒素与肺损伤有关，过量的内毒素可导致该模型发生肺泡出血。 (C) 1996 年，美国血液学会。
Idiopathic pneumonia syndrome (IPS) refers to diffuse, noninfectious pneumonia that occurs after allogeneic bone marrow transplantation (BMT). We have developed a model of IFS using a well-characterized murine BMT system (B10.BR --> CBA) in which lung injury after BMT can be induced by minor histocompatibility (H) antigenic differences between donor and host. Lung pathology and broncho-alveolar lavage (BAL) fluid were analyzed in transplant recipients before and after both syngeneic and allogeneic BMT. At 2 weeks after BMT, no specific pathologic abnormalities were noted; at 6 weeks, both pneumonitis and mononuclear cell infiltration around vessels and bronchioles were observed only in mice receiving allogeneic BMT, This injury was associated with elevated BAL fluid levels of endotoxin (lipopolysaccharide [LPS]), neutrophils, and tumor necrosis factor alpha. No pathologic organisms were isolated from the respiratory tract of any animal. We also tested the role of endotoxin in the development of this injury. Injection of LPS 6 weeks after transplantation caused profound lung injury only in mice with moderate graft-versus-host disease; dramatic increases in BAL neutrophils and tumor necrosis factor alpha were observed, with alveolar hemorrhage occurring in 4 of 12 of these mice but in no other group. We conclude that (1) this murine BMT system is a potentially useful model of clinical IPS; (2) minor H differences between donor and recipient can be important stimuli in the pathogenesis of IPS; and (3) endotoxin in BAL fluid is associated with lung injury, and excess endotoxin can cause the development of alveolar hemorrhage in this model. (C) 1996 by The American Society of Hematology.