Hydrogen peroxide and superoxide modulate leukocyte adhesion molecule expression and leukocyte endothelial adhesion

Abstract

While endothelial oxidant generation and subsequent leukocyte chemotaxis and activation are important mechanisms of tissue damage in ischemic organs, it is not known if oxidant generation may be involved in triggering the subsequent leukocyte-mediated injury which occurs. Questions remain whether particular oxidants and oxygen-free radicals are capable of modulating the expression of leukocyte adhesion molecules and effecting leukocyte endothelial adhesion. Studies were performed to determine the effect of different biologically occurring oxidant molecules and oxygen free radicals including: .O2-, .OH, and H2O2 on the expression of integrin and selectin adhesion molecules on the surface of human PMNs and to determine the effect of these alterations on PMN adhesion to the endothelium. Adhesion molecule expression on the surface of human PMNs was measured by immunofluorescence flow cytometry. Electron paramagnetic resonance spectroscopy was applied to characterize the presence of exogenous free radical generation as well as that from activated PMNs. It was observed that these oxidants can cause up-regulation of CD11b and CD18 expression with shedding of L-selectin. The kinetics and dose-response of these effects were analyzed and their functional significance determined by measuring PMN adhesion to cultured human aortic endothelial monolayers. These studies demonstrate that oxygen free radicals and non-radical oxidants can directly trigger PMN activation and adhesion to vascular endothelium.

Serum Proteins Modified by Neutrophil-Derived Oxidants as Mediators of Neutrophil Stimulation

“…Indeed, exposure of PMN to H 2 O 2 in the absence of protein resulted in a dose-dependent CD11b and CD66b up-regulation, starting at a H 2 O 2 concentration of 100 M. This is compatible with an earlier study that reported on increased neutrophil ␤ 2 integrin expression by similar amounts of H 2 O 2 (11). Importantly, the presence of either C4 or HSA considerably triggered H 2 O 2 -dependent CD11b/CD66b upregulation, especially at H 2 O 2 concentrations that were too low to modulate receptor expression in the absence of protein.…”

“…Various oxidants were found to modulate the expression of neutrophil adhesion molecules and opsonic receptors and to increase PMN adhesion to endothelial cells (11)(12)(13). In addition, ROI are able to activate complement factor C5 in a nonenzymatic way, generating either C5b-like activity without C5 cleavage (14) or anaphylatoxins (15) depending on the ROI species studied.…”

Neutrophil migration during endotoxemia

“…Specifically, oxidant production, filamentous actin formation, mobilization of CD11b/CD18, and adhesion frequently happen simultaneously in activated PMNs [126,159,160]. Moreover, agents that activate oxidative and adhesive pathways concomitantly inhibit chemotactic responses of PMNs in vitro [161][162][163].…”

COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

“…It has been demonstrated that H 2 O 2 enhanced production could also stimulate neutrophils chemotaxis (25) , activate T lymphocyte (36) , and induce adhesion molecules expression (15) . Catalase transforms H 2 O 2 in H 2 O and O 2 , thus it must follow SOD increase to yield inert products (27) .…”