Role of CXC chemokines in pulmonary alveolar injury under mechanical stress

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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.