Differential role for T cells in the development of fibrotic lesions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus acute respiratory distress syndrome
Differential role for T cells in the development of fibrotic lesions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus acute respiratory distress syndrome
复制标题
DOI：
10.1165/rcmb.4891
复制
发表时间：
2003-02-01
影响因子：
6.4
通讯作者：
London, L
中科院分区：
文献类型：
--
作者：
Majeski, EI;Harley, RA;London, L
闭塞性细支气管炎机化性肺炎（BOOP）和急性呼吸窘迫综合征（ARDS）是两种具有纤维化成分的肺部疾病。BOOP的特征是血管周围/细支气管周围白细胞浸润，导致肺泡下纤维化的发展。ARDS是一种双相疾病，包括急性期和慢性期，急性期由严重的白细胞浸润、水肿、出血和透明膜形成组成，慢性期的特征在于持续的肺泡下和间质纤维化。感染1 X 106空斑形成单位（pfu）呼肠孤病毒1/L的CBA/J小鼠发生与BOOP相似的滤泡性细支气管炎和肺泡下纤维化。相反，感染1 × 107 pfu呼肠孤病毒1/L的CBA/J小鼠出现ARDS的组织学特征，包括弥漫性肺泡损伤、透明膜和肺泡内纤维化。在这份报告中，我们证明了T淋巴细胞在BOOP与ARDS相关的纤维化发展中的不同作用。新生期切除胸腺的CBA/J小鼠感染1 × 10（7）pfu（ARDS）呼肠孤病毒1/L后仍会出现ARDS的标志性特征，包括严重的病毒性肺炎，伴有主要由巨噬细胞和中性粒细胞组成的细胞浸润、透明膜形成和疾病急性期出血，以及疾病慢性期持续的肺泡下纤维化。相比之下，用1 × 106 pfu（BOOP）呼肠孤病毒1/L感染的经腹腔切除胸腺的CBA/J小鼠不会发生与BOOP相关的肺泡下纤维化。因此，虽然T细胞是BOOP相关的管腔内纤维化发展所必需的，但它们不是ARDS相关的管腔内纤维化发展所必需的。此外，我们认为干扰素-γ在纤维化过程中起着关键作用，并且干扰素-γ水平升高与从最轻到更严重的纤维化的连续性相关。
Bronchiolitis obliterans organizing pneumonia (BOOP) and Acute Respiratory Distress Syndrome (ARDS) are two pulmonary diseases with fibrotic components. BOOP is characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of infra-alveolar fibrosis. ARDS is a biphasic disease that includes an acute phase, consisting of severe leukocyte infiltration, edema, hemorrhage, and the formation of hyaline membranes, and a chronic phase, which is characterized by persistent infra-alveolar and interstitial fibrosis. CBA/J mice infected with 1 X 106 plaque-forming units (pfu) reovirus 1/L develop follicular bronchiolitis and infra-alveolar fibrosis similar to BOOP. In contrast, CBA/J mice infected with 1 X 107 pfu reovirus 1/L develop histologic characteristics of ARDS including diffuse alveolar damage, hyaline membranes, and intra-alveolar fibrosis. In this report, we demonstrate a differential role for T lymphocytes in the development of fibrosis associated with BOOP versus ARDS. Neonatally thymectomized CBA/J mice infected with 1 X 10(7) pfu (ARDS) reovirus 1/L still develop the hallmark characteristics of ARDS, including a severe viral pneumonia with cellular infiltrates comprised mainly of macrophages and neutrophils, hyaline membrane formation, and hemorrhage during the acute phase of the disease and persistent infra-alveolar fibrosis during the chronic phase of the disease. In contrast, neonatally thymectomized CBA/J mice infected with 1 X 106 pfu (BOOP) reovirus 1/L do not develop infra-alveolar fibrosis associated with BOOP. Therefore, while T cells are necessary for the development of intraluminal fibrosis associated with BOOP, they are not necessary for the development of intraluminal fibrosis associated with ARDS. Furthermore, we suggest that interferon-gamma plays a key role in the fibrotic process and that elevated levels of interferon-gamma are associated with a continuum from least to more severe fibrosis.