Adenosine attenuates the lipopolysaccharide (LPS) induced endothelial barrier dysfunction in murine model of acute lung injury

Abstract

RationaleAcute lung injury (ALI) affects approximately 200,000 people in the United States every year. A basic cause is pulmonary endothelial cell (EC) barrier disruption and the ensuing inflammation and increased permeability of the EC. Our previous studies on the human pulmonary arterial endothelial cells have shown that adenosine (AD), an endogenous purine nucleoside, attenuates the EC barrier. The goal of our experiments was to evaluate AD attenuation on the EC barrier in LPS treated mice.ResultsOur preliminary data indicate that mice challenged with LPS demonstrated an inflammatory response typical for ALI compared with normal saline (NS) treated controls. Microscopic examination of bronchoalveolar (BAL) showed fewer neutrophils in control and LPS/AD treated mice compared to LPS challenged mice. Protein and EBD extravasation analysis showed a decrease in the LPS/AD treated mice compared to LPS alone.ConclusionsAD attenuated the LPS‐induced permeability increase as evidenced by decreased leakage of protein and in the BAL and EBD extravasation into the lung. In addition, AD also decreased lung inflammation measured by BAL neutrophil cell counts. Further studies into the AD‐mediated signaling mechanisms in protecting the EC barrier may help elucidate the molecular pathways involved in EC barrier regulation. This work was supported by NIHLBI grant HL 083327 (ADV) and MCG PSRP grant (NSU).