Endothelial selectin blockade attenuates lung permeability of experimentalacid aspiration

Background. A central role for the polymorphonuclear leukocyte (PMN) in exp erimental acid aspiration, has been demonstrated by the observation that PM N depletion reduced pulmonary vascular permeability. This study investigate s the role of recombinant soluble P-selectin glycoprotein ligand-immunoglob ulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist in moderatin g acid aspiration lung injury. Methods. Tracheostomy tubes were placed in male C57BL/6 mice and 0.1 N HCl was instilled into the trachea at 2 mL/g after intravenous injection of I-1 25-albumin. After 4 hours the lung vascular permeability index (PI) and PMN accumulation in the bronchoalveolar lavage fluid were assessed. Results. PI in neutropenic mice was 63% reduced compared with the untreated group and similar to the PI of mice treated with 2 mg/kg rPSGL-Ig before a cid aspiration. PMN count of 19 +/- 5 in the bronchoalveolar lavage fluid i n rPSGL-Ig treated mice was significantly less than the untreated group PMN count of 586 +/- 72. The respective PI in mice treated with rPSGL-Ig 1/2 h our and 1 hour after acid aspiration was 45% and 39% reduced compared with the untreated group. Conclusions. Endothelial selectin blockade is as effective as PMN depletion in moderating acid aspiration induced lung permeability. Delayed antiselec tin therapy can decrease lung injury.