Eotaxin expression in sephadex-induced lung injury in rats

The CC chemokine eotaxin is a potent and specific eosinophil chemoattractan t. Eosinophil-dependent tissue injury has been shown to contribute to airwa y inflammation such as that in asthma. In the present study, We investigate d eotaxin expression in a rat model of pulmonary inflammation (featuring ac cumulation of eosinophils) induced by intratracheal instillation of cross-l inked dextran beads (Sephadex G200). Intratracheal instillation of 5 mg/kg Sephadex caused a time-dependent eosinophil infiltration into the lung, rea ching a peak at 24 hours. Eotaxin mRNA. in the lung paralleled the eosinoph il influx. Eotaxin protein in bronchoalveolar (BAL) fluids and lung homogen ates was shown by Western blot and immunostaining:to be maximally expressed by 24 hours. Sephadex-induced lung injury, as measured by I-125-labeled al bumin leakage from the pulmonary vasculature, developed in a time-dependent manner. Intravenous injection of blocking antibody to eotaxin significantl y decreased eosinophil infiltration and lung permeability. These data sugge st that, in the Sephadex model of lung inflammation, eotaxin upregulation m ediates intrapulmonary accumulation of eosinophils and the development of l ung injury.