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Reactive oxidant species (ROS) release from fMLP-stimulated neutrophils increases microvessel permeability via nitric oxide (NO)-cGMP-dependent pathway.
Zhu-L; Castranova-V; He-P
FASEB J 2004 Mar; 18(4)(Suppl):A245
Our previous study demonstrated that ROS release from fMLP-stimulated neutrophils increases microvessel permeability independently from leukocyte adhesion and migration. We hypothesized that the activation of NO-cGMP-dependent signaling pathway in endothelial cells is the mechanism and that enhancing endothelial cAMP levels may overcome its activation and prevent the ROS-induced permeability increase. ROS production from fMLP-stimulated rat neutrophils was quantified by measuring chemiluminescence. Changes in permeability after microvessels were perfused with fMLP-stimulated neutrophil suspensions with and without the inhibition of endothelial eNOS or guanylate cyclase were measured as hydraulic conductivity in individually perfused rat mesenteric venular microvessels. The application of guanylate cyclase inhibitor, LY-83583, did not reduce the ROS release from fMLP stimulated neutrophils, but abolished ROS-induced permeability increase. Similar results were obtained with inhibition of endothelial eNOS activity by internalization of caveolin-1 scaffolding domain in individually perfused microvessels. Enhancing endothelial cAMP levels by the application of an beta-adrenergic agonist, isoproteronol, prevented the permeability increase. These results indicate that ROS-induced increases in microvessel permeability involve the activation of a NO-cGMP-dependent signaling pathway, which can be counteracted by enhancing endothelial cAMP levels.
Cell-function; Cell-metabolism; Cell-transformation; Cell-wall-permeability; Chemical-hypersensitivity; Chemical-properties; Gas-adsorption
Issue of Publication
The FASEB Journal. Experimental Biology 2004, Washington, DC, April 17-21, 2004
Page last reviewed: May 5, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division