Role of Stem Cell Factor and Bone Marrow-Derived Fibroblasts in Airway Remodeling
Role of Stem Cell Factor and Bone Marrow-Derived Fibroblasts in Airway Remodeling
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DOI：
10.2353/ajpath.2009.080513
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发表时间：
2009-02-01
影响因子：
6
通讯作者：
Phan, Sem H.
中科院分区：
文献类型：
--
作者：
Dolgachev, Vladislav A.;Ullenbruch, Matthew R.;Phan, Sem H.
最近的证据表明，骨髓来源的成纤维细胞参与哮喘气道重塑，但这些成纤维细胞的作用和招募机制仍不清楚。干细胞因子（SCF）是造血干细胞增殖的关键因子，在气道重塑过程中也很重要。为了检验 SCF 参与骨髓源性祖细胞的募集和分化的假设，创建了 GFP-骨髓嵌合小鼠。然后对这些小鼠进行致敏并用蟑螂抗原进行长期攻击，以诱导慢性气道疾病。荧光显微镜显示这些小鼠的气道中有大量表达 GFP 的成纤维细胞涌入，这通过对共表达 GFP 和胶原蛋白 I 的细胞进行流式细胞术分析得到证实。与对照肺源性成纤维细胞相比，这些细胞优先表达 c-kit、白细胞介素 31 受体和端粒酶逆转录酶。有趣的是，SCF 刺激骨髓细胞中白细胞介素 31 受体的表达，而白细胞介素 31 强烈诱导成纤维细胞中端粒酶逆转录酶的表达。使用 SCF 中和抗体治疗可显着减少气道重塑，并抑制这些骨髓来源的细胞向肺部的募集。因此，SCF 与白细胞介素 31 结合可能通过促进骨髓来源的成纤维细胞前体募集到肺中，从而在气道重塑中发挥重要作用，并具有促进肺肌成纤维细胞分化的能力。 (Am J Pathol 2009, 174:390-400; DOI: 10.2353/ajpath.2009.080513)
Recent evidence suggests that bone marrow-derived fibroblasts are involved in air-way 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. (Am J Pathol 2009, 174:390-400; DOI: 10.2353/ajpath.2009.080513)