Focus on carbon monoxide: a modulator of neutrophil oxidants and elastase spatial localization?

Abstract

GASEOUS SIGNAL MEDIATORS include nitric oxide (NO), hydrogen sulfide, and carbon monoxide (CO) (3, 20, 35). Both NO and hydrogen sulfide play important roles in inflammation, with the existing evidence supporting them as components of the normal biochemical milieu that stabilize the vasculature against leukocyte adhesion, extravasation, and vascular permeability (25, 35). Unlike G protein-coupled receptors, gasotransmitters are membrane-permeant gases that modulate several forms of cell signaling by chemically binding numerous intracellular targets (25, 26, 35, 36). CO is formed in several tissues through the action of two types of hemoxygenases (HOs): an inducible form HO-1 and constituitive forms HO-2 and -3 (HO-3 is involved in O2 sensing) (19). HO-1 is the 32-kDa form of HO, synthesized in response to heat stress (hence, heat shock protein32), oxidants, cytokines, and environmental stress (e.g., metals). HOs catabolize heme to bilivervidin (rapidly converted to bilirubin by biliverdin reductase), Fe 2 , and CO. While biliverdin and bilirubin formed by HO-1 and -2 are major antioxidants, with potency comparable with glutathione, many studies suggest that the induction of HO-1 expression in inflammation is adaptive through CO-mediated effects. CO is a potent physiological regulator of vascular tone, like NO, and exhibits some similar properties. For example, CO