CARBON-MONOXIDE ENHANCES HUMAN NEUTROPHIL MIGRATION IN A CYCLIC GMP-DEPENDENT WAY

Carbon monoxide (CO) enhanced random migration of human neutrophils. A n optimally stimulatory effect was observed with 10 mu M CO. CO caused a rapid and transient increase in intracellular level of guanosine-3' ,5'-cyclic monophosphate (cGMP). The enhancing effect of CO on random migration was reversed to a large extent by inhibitors of cGMP accumul ation, and by antagonists of cGMP-dependent protein kinase (G-kinase). These results strongly suggest that the enhancement of random migrati on by CO is mediated by cGMP and G-kinase. Using hemoglobin, a scaveng er of CO, we could show that stimulation of soluble guanylate cyclase over an extended period of time, rather than the observed fast and tra nsient increase in intracellular cGMP levels, is responsable for CO-ac tivated migration. We postulate that CO, like nitric oxide (NO), acts as a biological signal in the immune system. (C) 1996 Academic Press, Inc.