Bone marrow-derived progenitor cells in pulmonary fibrosis.
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.
Hashimoto
Naozumi
N
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Jin
Hong
H
Liu
Tianju
T
Chensue
Stephen W
SW
Phan
Sem H
SH
D000199:Actins / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008024:Ligands; D008164:Luminescent Proteins / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011658:Pulmonary Fibrosis / Q000473:pathology*; D012313:RNA / Q000378:metabolism; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000473:pathology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000199:Actins; D000964:Antimetabolites, Antineoplastic; C515371:Ccr7 protein, mouse; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D008024:Ligands; D008164:Luminescent Proteins; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D049452:Green Fluorescent Proteins; D012313:RNA; D003094:Collagen