Washed human platelets prevent ischemia-reperfusion edema in isolated rabbit lungs

Abstract

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.

Nitric oxide production and perivascular nitration in brain after carbon monoxide poisoning in the rat.

“…Hence, mechanisms unrelated to platelet-derived oxidants must cause nitrotyrosine formation during the hourlong exposures. In this situation, platelets appear to antagonize the oxidative process; a phenomenon reported in several models of oxidative stress (24,25). The concentration of nitrotyrosine was the same whether rats were exposed to 1000 ppm CO for 1 h or to the full, standard CO model which involved exposure to 1000 ppm for 40 min and then to 3000 ppm for 20 min (Fig.…”

Platelet mass index and prediction of severity of transient tachypnea of the newborn

“…25 Platelets preserve the normal endothelial permeability in the lungs exposed to ischemia-reperfusion injury by releasing platelet glutathione redox cycle antioxidants. 26 Lo et al noted an increase in pulmonary vascular permeability in animals with thrombocytopenia. 27 Platelets limit the transfer of water, proteins, and red blood cells out of the vessels by contributing to the basal barrier integrity of the alveolar capillaries.…”

“…Platelets have antioxidant effects, and antioxidant‐intact platelets decrease oxidant‐induced lung edema by preventing increased membrane permeability . Platelets preserve the normal endothelial permeability in the lungs exposed to ischemia–reperfusion injury by releasing platelet glutathione redox cycle antioxidants . Lo et al .…”

Platelets in Lung Biology

“…In a study of isolated sheep lungs, perfusion with platelet-free solutions worsened lung fluid accumulation, indicating that platelets protect against pulmonary edema by an unknown mechanism (68). In isolated perfused rabbit lungs, human platelets reduced lung edema induced by oxidant challenge or by ischemia-reperfusion (69, 70). In vitro studies also demonstrated that intact platelets reduce labeled-albumin transfer across cultured pulmonary artery endothelial monolayers (65).…”