Role of CXC chemokines in pulmonary alveolar injury under mechanical stress

1.大鼠呼吸机诱导的肺损伤（VILI）模型大鼠以潮气量（TV）10 ml/kg BW（低TV）或30 ml/kg BW（高TV）机械通气3 h。高TV组大鼠出现肺淤血、肺泡出血和中性粒细胞浸润，提示高TV可诱发VILI。在CXC趋化因子组中，高TV组支气管肺泡灌洗液（BALF）中的中性粒细胞趋化因子-1（CINC-1）浓度显著高于低TV组（p<0.05）。免疫组化显示CINC-1在外周气道和肺泡上皮细胞表达。高TV组CINC-1 mRNA表达也明显增强.抗CINC-1抗体对VILI的影响用50、100、200和500μg/体浓度的兔抗大鼠CINC-1多克隆抗体预处理以剂量依赖性方式显著抑制VILI;组织学发现改善，BALF蛋白浓度降低，BALF中性粒细胞计数降低。死亡率降低。BALF中CINC-1浓度的增加也被抑制，证实了抗体的中和作用.大鼠肺泡Ⅱ型上皮细胞在机械压力作用下产生CINC-1的研究用50cmH_2O、15次/min的压力作用于分离的肺泡Ⅱ型上皮细胞3小时，可显著增加培养液中CINC-1的含量。用类固醇预处理减少了CINC-1的产生，但对类固醇处理的细胞的压力负荷再次诱导CINC-1浓度的增加。II型细胞产生CINC-1响应机械应力，如压力。

1. Rat ventilator-induced lung injury (VILI) modelRats were mechanically ventilated with a tidal volume (TV) of either 10ml/kg BW (low TV) or 30ml/kg BW (high TV) for 3 hours. Congestion, alveolar bleeding and neutrophil infiltration were observed in rats of high TV, indicating that VILI was induced in this TV. Among the group of CXC chemokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1) concentration in broncho-alveolar lavage fluid (BALF) was significantly higher in the high TV group than the low TV group (p<0.05). Immunohistochemistry showed that CINC-1 was expressed in peripheral airways and alveolar epithelial cells. Expression of CINC-1 mRNA was also augmented in the high TV group.2. Effects of anti-CINC-1 antibodies on VILIPre-treatment with a rabbit anti-rat CINC-1 polyclonal antibody at concentrations of 50, 100, 200 and 500μg/body significantly inhibited VILI in a dose-dependent manner ; histological findings improved, BALF protein concentration reduced and BALF neutrophil count decreased. Mortality rate was reduced. The increase in BALF CINC-1 concentration in VILI was also inhibited, confirming the neutralizing effect of the antibody.3. CINC-1 production in rat alveolar type II cells under mechanical stressPressure load of 50cmH_2O, 15 times/min for 3 hours on isolated type II cells significantly increased CINC-1 concentration in the culture medium. Pretreatment with steroid reduced CINC-1 production, but the pressure load on steroid treated cells again induced an increase in CINC-1 concentration. Type II cells produced CINC-1 in response to mechanical stress such as pressure.