Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice.
The incidence of pulmonary fibrosis increases with age. Studies from our group have implicated circulating progenitor cells, termed fibrocytes, in lung fibrosis. In this study, we investigate whether the preceding determinants of inflammation and fibrosis were augmented with aging. We compared responses to intratracheal bleomycin in senescence-accelerated prone mice (SAMP), with responses in age-matched control senescence-accelerated resistant mice (SAMR). SAMP mice demonstrated an exaggerated inflammatory response as evidenced by lung histology. Bleomycin-induced fibrosis was significantly higher in SAMP mice compared with SAMR controls. Consistent with fibrotic changes in the lung, SAMP mice expressed higher levels of transforming growth factor-beta1 in the lung. Furthermore, SAMP mice showed higher numbers of fibrocytes and higher levels of stromal cell-derived factor-1 in the peripheral blood. This study provides the novel observation that apart from increases in inflammatory and fibrotic factors in response to injury, the increased mobilization of fibrocytes may be involved in age-related susceptibility to lung fibrosis.
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Jianguo
J
Xu
Edilson T
ET
Gonzalez
Smita S
SS
Iyer
Valerie
V
Mac
Ana L
AL
Mora
Roy L
RL
Sutliff
Alana
A
Reed
Kenneth L
KL
Brigham
Patricia
P
Kelly
Mauricio
M
Rojas
D000375:Aging / Q000187:drug effects; D000818:Animals; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D001854:Bone Marrow Cells / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D024042:Collagen Type I; D024141:Collagen Type IV; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D006909:Hydroxyproline