Role of stem cell factor and bone marrow derived fibroblasts in airway remodeling. (140.1)

Autor: Vladislav Dolgachev, Matthew R Ullenbruch, Nicholas W Lukacs, Sem H Phan
Rok vydání: 2009
Předmět:
Zdroj: The Journal of Immunology. 182:140.1-140.1
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.182.supp.140.1
Popis: Recent evidence suggests involvement of bone marrow derived fibroblasts in airway remodeling in asthma, but their role and the mechanism of recruitment remain unclear. Stem cell factor (SCF), a key factor in the propagation of hematopoietic stem cells, is important in airway remodeling. To test the hypothesis that SCF is involved in the recruitment and differentiation of these bone marrow derived progenitor cells, GFP bone marrow chimera mice were created. These mice were then sensitized and chronically challenged with cockroach antigen (CRA) to induce chronic airway disease. Fluorescence microscopy revealed the influx of significant numbers of GFP expressing fibroblasts in these airways, which was confirmed by flow cytometric analysis for cells co-expressing GFP and collagen I. These cells preferentially expressed c-kit, IL-31 receptor and telomerase reverse transcriptase when compared to lung-derived fibroblasts. Interestingly, SCF stimulated IL-31 receptor expression in bone marrow cells, while IL-31 strongly induced telomerase reverse transcriptase expression in fibroblasts. Treatment with neutralizing antibodies to SCF significantly reduced airway remodeling and suppressed recruitment of these bone marrow-derived cells to the lung. Thus SCF in conjunction with IL-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.
Databáze: OpenAIRE