The protective effect of adenosine triphosphate-MgCl2 on ischemia-reperfusion lung injury is leukocyte dependent.
Adenosine triphosphate (ATP)-MgCl(2) attenuates ischemia-reperfusion (I-R)-induced lung injury in rats. A previous study indirectly suggests 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 ATP-MgCl(2). This study investigated the role of leukocytes in I-R injury and the protective effect of ATP-MgCl(2) 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-MgCl(2) 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-MgCl(2) (1 x 10(-6)M) together with leukocytes (2.9 x 10(6)/ml in the perfusate) but not with ATP-MgCl(2) alone. Our data suggest that I-R-induced acute lung injury is not dependent on circulating leukocytes. Pretreatment with ATP-MgCl(2) plus leukocytes but not ATP-MgCl(2) 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-MgCl(2) requires the presence of leukocytes.
Chen
Wei-Teing
WT
Tri-Service General Hospital, No. 325, Sec. 2 Cheng-Kung Road, Neihu 114, Taipei, Taiwan, ROC.
Huang
Wen-Hsin
WH
Wang
David
D
Yu
Fu-Chiu
FC
Chi
Ying-Chih
YC
Wu
Jen-Chine
JC
Wu
Kerry
K
Perng
Wann-Cherng
WC
Wu
Chin-Pyng
CP
Yan
Horng-Chin
HC
D000255:Adenosine Triphosphate / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D011669:Pulmonary Wedge Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D000255:Adenosine Triphosphate