Asakura S, Colby T V, Limper A H
The Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota, USA.
Am J Respir Crit Care Med. 1996 Nov;154(5):1525-30. doi: 10.1164/ajrccm.154.5.8912775.
Pulmonary eosinophilic granuloma is characterized by infiltration of the lungs with fibronodular lesions containing specialized Langerhans' cells. In some patients, progressive pulmonary fibrosis leads to significant respiratory impairment. Transforming growth factor-beta1 (TGF-beta1) promotes fibrosis by enhancing the synthesis of extracellular matrix components. The role of TGF-beta1 in promoting fibrosis in the setting of pulmonary eosinophilic granuloma is currently unknown. We used immunohistochemistry to evaluate the extent and distribution of TGF-beta1 and the extracellular matrix components type I collagen and decorin, a TGF-beta1-binding proteoglycan. Lung biopsies from 11 patients with pulmonary eosinophilic granuloma were evaluated. In biopsies with active inflammatory lesions containing Langerhans' cells, hyperplastic type 2 pneumocytes and alveolar macrophages within and surrounding the fibronodular lesions contained abundant TGF-beta1. Langerhans' cells were consistently devoid of immunoreactive TGF-beta1. Active inflammatory lesions also exhibited staining for decorin, in a loosely organized distribution. Advanced fibrotic lesions of eosinophilic granuloma, containing minimal inflammatory cells and few or no Langerhans' cells, exhibited weak or absent staining for TGF-beta1 within either hyperplastic type 2 pneumocytes or alveolar macrophages. The fibroconnective tissues of these advanced fibrotic lesions consistently revealed dense staining for decorin. Through their actions on extracellular matrix protein accumulation, TGF-beta1 and the TGF-beta1-binding proteoglycan decorin may modulate fibrotic repair accompanying pulmonary eosinophilic granuloma.
肺嗜酸性肉芽肿的特征是肺内出现含有特殊朗格汉斯细胞的纤维结节性病变浸润。在一些患者中,进行性肺纤维化会导致严重的呼吸功能损害。转化生长因子-β1(TGF-β1)通过增强细胞外基质成分的合成来促进纤维化。TGF-β1在肺嗜酸性肉芽肿情况下促进纤维化中的作用目前尚不清楚。我们使用免疫组织化学来评估TGF-β1以及细胞外基质成分I型胶原蛋白和核心蛋白聚糖(一种与TGF-β1结合的蛋白聚糖)的范围和分布。对11例肺嗜酸性肉芽肿患者的肺活检组织进行了评估。在含有朗格汉斯细胞的活动性炎性病变活检组织中,纤维结节性病变内及周围的增生性II型肺细胞和肺泡巨噬细胞含有丰富的TGF-β1。朗格汉斯细胞始终缺乏免疫反应性TGF-β1。活动性炎性病变中核心蛋白聚糖也呈染色,分布松散。嗜酸性肉芽肿的晚期纤维化病变,含有极少的炎性细胞且很少或没有朗格汉斯细胞,在增生性II型肺细胞或肺泡巨噬细胞内TGF-β1染色较弱或无染色。这些晚期纤维化病变的纤维结缔组织始终显示核心蛋白聚糖染色浓密。通过它们对细胞外基质蛋白积累的作用,TGF-β1和与TGF-β1结合的蛋白聚糖核心蛋白聚糖可能调节伴随肺嗜酸性肉芽肿的纤维化修复。