Bone marrow-derived progenitor cells in pulmonary fibrosis.
Bone marrow-derived progenitor cells in pulmonary fibrosis.
复制标题
DOI：
10.1172/jci18847
复制
发表时间：
2004-01
期刊：
影响因子：
--
通讯作者：
N. Hashimoto;Hong Jin;Tianju Liu;S. Chensue;S. Phan
中科院分区：
文献类型：
--
作者：
N. Hashimoto;Hong Jin;Tianju Liu;S. Chensue;S. Phan
肺纤维化中成纤维细胞的起源被认为是肺内的，但不排除其起源于肺外，尤其是来源于骨髓(BM)前体细胞。为了直接检验这种可能性，成年小鼠被持久地植入从表达增强GFP的转基因小鼠中分离出来的BM。气管内注射博莱霉素(BLM)诱导嵌合体小鼠肺纤维化，在活动性纤维化病变中出现大量GFP(+)细胞，而在对照肺中仅可检测到少量GFP(+)细胞。对肺细胞的流式细胞术分析证实了博莱曼诱导嵌合体小鼠GFP(+)细胞的增加，并显示也表达I型胶原的GFP(+)细胞显著增加。从嵌合体小鼠分离的GFP(+)肺成纤维细胞表达胶原和端粒酶逆转录酶，但不表达α-平滑肌肌动蛋白。用转化生长因子-β处理分离的GFP(+)成纤维细胞不能诱导肌成纤维细胞分化。培养的肺成纤维细胞表达趋化因子受体CXCR4和CCR7，并分别对其同源配体、基质细胞衍生因子-1α和次级淋巴趋化因子产生化学反应。因此，肺纤维化中产生胶原的肺成纤维细胞也可以从BM祖细胞分化而来。
The origin of fibroblasts in pulmonary fibrosis is assumed to be intrapulmonary, but their extrapulmonary origin and especially derivation from bone marrow (BM) progenitor cells has not been ruled out. To examine this possibility directly, adult mice were durably engrafted with BM isolated from transgenic mice expressing enhanced GFP. Induction of pulmonary fibrosis in such chimera mice by endotracheal bleomycin (BLM) injection caused large numbers of GFP(+) cells to appear in active fibrotic lesions, while only a few GFP(+) cells could be identified in control lungs. Flow-cytometric analysis of lung cells confirmed the BLM-induced increase in GFP(+) cells in chimera mice and revealed a significant increase in GFP(+) cells that also express type I collagen. GFP(+) lung fibroblasts isolated from chimera mice expressed collagen and telomerase reverse transcriptase but not alpha-smooth muscle actin. Treatment of isolated GFP(+) fibroblasts with TGF-beta failed to induce myofibroblast differentiation. Cultured lung fibroblasts expressed the chemokine receptors CXCR4 and CCR7 and responded chemotactically to their cognate ligands, stromal cell-derived factor-1 alpha and secondary lymphoid chemokine, respectively. Thus the collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells.