Role of stem cell factor and bone marrow-derived fibroblasts in airway remodeling.
Recent evidence suggests that bone marrow-derived fibroblasts are involved in airway remodeling in asthma, but the role and mechanism of recruitment of these fibroblasts remains unclear. Stem cell factor (SCF), a key factor in the propagation of hematopoietic stem cells, is important in the process of airway remodeling as well. To test the hypothesis that SCF is involved in the recruitment and differentiation of bone marrow-derived progenitor cells, GFP-bone marrow chimeric mice were created. These mice were then sensitized and chronically challenged with cockroach antigen to induce chronic airway disease. Fluorescence microscopy revealed an influx of significant numbers of GFP-expressing fibroblasts in the airways of these mice, which was confirmed by flow cytometric analysis of cells co-expressing both GFP and collagen I. These cells preferentially expressed c-kit, interleukin-31 receptor, and telomerase reverse transcriptase when compared with control lung-derived fibroblasts. Interestingly, SCF stimulated interleukin-31 receptor expression in bone marrow cells, whereas interleukin-31 strongly induced telomerase reverse transcriptase expression in fibroblasts. Treatment with neutralizing antibodies to SCF significantly reduced airway remodeling and suppressed the recruitment of these bone marrow-derived cells to the lung. Thus SCF in conjunction with interleukin-31 may play a significant role in airway remodeling by promoting the recruitment of bone marrow-derived fibroblast precursors into the lung with the capacity to promote lung myofibroblast differentiation.
Dolgachev
Vladislav A
VA
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA. vdolgach@med.umich.edu
Ullenbruch
Matthew R
MR
Lukacs
Nicholas W
NW
Phan
Sem H
SH
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology*; D005434:Flow Cytometry; D015870:Gene Expression; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D018183:Transplantation Chimera
D007378:Interleukins; D019089:Stem Cell Factor; C502588:interleukin-31, mouse; D019009:Proto-Oncogene Proteins c-kit; D019098:Telomerase; C509187:Tert protein, mouse