Washed human platelets prevent ischemia-reperfusion edema in isolated rabbit lungs.
Washed human platelets prevent edema formation in isolated rabbit lungs infused with xanthine oxidase, an enzyme that injures endothelial membranes by generating extracellular oxidants. We hypothesized that platelets would similarly preserve membrane permeability in isolated lungs exposed to ischemia-reperfusion injury, a model that perturbs endothelial cells by the generation of intracellular oxidants. Isolated perfused rabbit lungs (IPL) were exposed to warm ischemia-reperfusion to cause lung edema. The infusion of washed human platelets (1.05 +/- 0.02 x 10(10) cells) prevented edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, histological edema, and preservation of paraendothelial cell tight junctions. Inhibition of the platelet glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, dehydroepiandrosterone, or 1-chloro-2,4-dinitrobenzene interfered with platelet protective effects. In contrast, inhibition of platelet catalase with aminotriazole and H2O2 had no effect on platelet protection. Lung tissue malonyldialdehyde concentrations were similar in isolated lungs exposed to ischemia-reperfusion with or without the infusion of platelets. These results indicate that platelet attenuation of ischemia-reperfusion lung edema depends on platelet glutathione redox cycle antioxidants but not platelet catalase.
Zamora
C A
CA
Department of Cell and Molecular Pharmacology, Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.
Baron
D
D
Heffner
J E
JE
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002374:Catalase / Q000097:blood; D005978:Glutathione / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000648:ultrastructure; D008854:Microscopy, Electron; D010084:Oxidation-Reduction; D011654:Pulmonary Edema / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*
D000975:Antioxidants; D002374:Catalase; D005978:Glutathione