The Protective Effect of Adenosine Triphosphate-MgCl₂ on Ischemia-Reperfusion Lung Injury Is Leukocyte Dependent

Abstract

Adenosine triphosphate (ATP)-MgCl₂ attenuates ischemia-reperfusion (I-R)-induced lung injury in rats. A previous study indirectly suggests that Mg²⁺-dependent ecto-ATPases on the surface of leukocytes are responsible for the hydrolysis of ATP-MgCl₂ to adenosine, which then contributes to the protective effect of ATP-MgCl₂. This study investigated the role of leukocytes in I-R injury and the protective effect of ATP-MgCl₂ in our buffer-perfused isolated rat lung model. After isolating the lung blood flow of adult male Sprague-Dawley rats, the lungs were perfused through the pulmonary artery cannula with a physiologic salt solution containing human serum albumin. The protective effect of ATP-MgCl₂ pretreatment with or without leukocytes was investigated. Capillary permeability (K_fc), lung weight gain (LWG), lung wet weight/body weight ratio (LW/BW), lung lavage protein concentration (LPC) and pulmonary artery pressure (PAP) were measured. I-R produced a significant increase in K_fc, LWG, LW/BW, LPC, and PAP. The increases in these indices were significantly attenuated by pretreatment with ATP-MgCl₂ (1 × 10^–6M) together with leukocytes (2.9 × 10⁶/ml in the perfusate) but not with ATP-MgCl₂ alone. Our data suggest that I-R-induced acute lung injury is not dependent on circulating leukocytes. Pretreatment with ATP-MgCl₂ plus leukocytes but not ATP-MgCl₂ alone had protective effects against I-R lung injury. Whether these findings occur in vivo could not be determined in this study. In our isolated lung red blood cell-free perfusate system, the protective effect of ATP-MgCl₂ requires the presence of leukocytes.

Biomedical Vignette

“…A previous study [14] indirectly suggested that Mg 2+ -dependent ecto-ATPases on the surface of leukocytes are responsible for the hydrolysis of ATP-MgCl 2 to adenosine, which then contributes to the protective effect of ATPMgCl 2 . Chen et al [7], in a buffer-perfused isolated rat lung model, found that ischemia-reperfusion increases capillary permeability, lung weight gain, wet lung/body weight ratio, lung lavaged protein concen-…”