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The mechanisms of reactive oxygen species (ROS) generation in neutrophils in monocrotoline-induced pulmonary arterial hypertension (MCT-PAH) were studied. MCT was injected subcutaneously to rats (60 mg/kg). FMLP-stimulated ROS generation and myeloperoxidase (MPO) secretion from neutrophils was measured using chemiluminescence. The involvement of the signal pathway components in the redox activation of cells was assessed using specific inhibitors of MPO, NADPH oxidase, phosphatidylinositol 3-kinase (PI3K) and cyclooxygenase (CO). It has been shown that initially (up to 28 days of MCT-PAH) ROS generation in rat neutrophils was decreased, which is associated with the decrease of NADPH oxidase activity and the increase of MPO secretion into the extracellular medium. However, at the last stage of MCT-PAH (60 days), ROS production was increased, which is due to MPO and NADPH oxidase activation and the decrease of CO and PI3K pathways contribution. To sum up, the intracellular signaling pathways involved in ROS generation in neutrophils are changing in depends of the pulmonary arterial hypertension stage. |
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