Bone marrow–derived progenitor cells in pulmonary fibrosis
Naozumi Hashimoto, … , Stephen W. Chensue, Sem H. Phan
Naozumi Hashimoto, … , Stephen W. Chensue, Sem H. Phan
Published January 15, 2004
Citation Information: J Clin Invest. 2004;113(2):243-252. https://doi.org/10.1172/JCI18847.
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Article Cell biology

Bone marrow–derived progenitor cells in pulmonary fibrosis

Abstract

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 α-smooth muscle actin. Treatment of isolated GFP+ fibroblasts with TGF-β 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-1α and secondary lymphoid chemokine, respectively. Thus the collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells.

Authors

Naozumi Hashimoto, Hong Jin, Tianju Liu, Stephen W. Chensue, Sem H. Phan

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Figure 3

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Morphology of BLM-induced lung fibrosis in BM chimera mice. Representati...
Morphology of BLM-induced lung fibrosis in BM chimera mice. Representative lung sections from BLM-treated (a–c) or saline-treated (d–f) GFP BM chimera mice were evaluated at day 28 after BLM or saline treatment. The H&E-stained sections revealed severe distortion of lung alveolar architecture due to extensive fibrosis (a and b, at ×40 and ×200, respectively). (c) Numerous GFP+ cells in densely cellular fibrotic lesions were easily identifiable by fluorescence microscopy in BLM-treated lungs. ×200. In contrast, H&E-stained lung sections from saline-treated GFP BM chimera mice showed normal lung architecture (d and e, at ×40 and ×200, respectively), with a few scattered GFP+ cells visualized by fluorescence microscopy (f, at ×200). Insets in c and f showed the light-microscopic appearance of the respective sections examined by fluorescence microscopy. ×200.