Bone marrow-derived progenitor cells in pulmonary fibrosis
Bone marrow-derived progenitor cells in pulmonary fibrosis
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DOI：
10.1172/jci200418847
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发表时间：
2004-01-01
影响因子：
15.9
通讯作者：
Phan, SH
中科院分区：
文献类型：
--
作者：
Hashimoto, N;Jin, H;Phan, SH
肺纤维化中成纤维细胞的起源被认为是肺内的，但它们的肺外起源，特别是来自骨髓（BM）祖细胞的来源尚未被排除。为了直接检查这种可能性，将成年小鼠持久地植入从表达增强的GFP的转基因小鼠分离的BM。通过气管内注射博莱霉素（BLM）诱导这种嵌合体小鼠的肺纤维化，导致大量GFP（+）细胞出现在活动性纤维化病变中，而在对照肺中只能鉴定到少数GFP（+）细胞。肺细胞的流式细胞术分析证实了BLM诱导的嵌合体小鼠中GFP（+）细胞的增加，并揭示了也表达I型胶原的GFP（+）细胞的显着增加。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TGF-β处理分离的GFP（+）成纤维细胞不能诱导成肌纤维细胞分化。培养的肺成纤维细胞表达趋化因子受体CXCR 4和CCR 7，并分别对它们的同源配体、基质细胞衍生因子-1 α和次级淋巴样趋化因子产生趋化反应。因此，肺纤维化中产生胶原的肺成纤维细胞也可以来源于BM祖细胞。
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-1alpha and secondary lymphoid chemokine, respectively. Thus the collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells.