Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Respir Physiol Neurobiol. 2011 Jan 31;175(1):153-63. doi: 10.1016/j.resp.2010.10.006. Epub 2010 Nov 2.
We hypothesized that bone marrow-derived mononuclear cells (BMDMC) would attenuate the remodeling process in a chronic allergic inflammation model. C57BL/6 mice were assigned to two groups. In OVA, mice were sensitized and repeatedly challenged with ovalbumin. Control mice (C) received saline under the same protocol. C and OVA were further randomized to receive BMDMC (2 × 10⁶) or saline intravenously 24 h before the first challenge. BMDMC therapy reduced eosinophil infiltration, smooth muscle-specific actin expression, subepithelial fibrosis, and myocyte hypertrophy and hyperplasia, thus causing a decrease in airway hyperresponsiveness and lung mechanical parameters. BMDMC from green fluorescent protein (GFP)-transgenic mice transplanted into GFP-negative mice yielded lower engraftment in OVA. BMDMC increased insulin-like growth factor expression, but reduced interleukin-5, transforming growth factor-β, platelet-derived growth factor, and vascular endothelial growth factor mRNA expression. In conclusion, in the present chronic allergic inflammation model, BMDMC therapy was an effective pre-treatment protocol that potentiated airway epithelial cell repair and prevented inflammatory and remodeling processes.
我们假设骨髓来源的单核细胞(BMDMC)将减轻慢性过敏炎症模型中的重塑过程。C57BL/6 小鼠被分为两组。在 OVA 组中,小鼠用卵清蛋白致敏并反复挑战。对照小鼠(C)在相同方案下接受生理盐水。C 和 OVA 进一步随机接受 BMDMC(2×10⁶)或生理盐水静脉注射,在第一次挑战前 24 小时。BMDMC 治疗减少了嗜酸性粒细胞浸润、平滑肌特异性肌动蛋白表达、黏膜下纤维化以及肌细胞肥大和增生,从而导致气道高反应性和肺力学参数降低。从绿色荧光蛋白(GFP)转基因小鼠移植到 GFP 阴性小鼠的 BMDMC 植入率较低。BMDMC 增加了胰岛素样生长因子的表达,但减少了白细胞介素 5、转化生长因子-β、血小板衍生生长因子和血管内皮生长因子 mRNA 的表达。总之,在本慢性过敏炎症模型中,BMDMC 治疗是一种有效的预处理方案,增强了气道上皮细胞修复并预防了炎症和重塑过程。