Carbon monoxide enhances human neutrophil migration in a cyclic GMP-dependent way.
Carbon monoxide (CO) enhanced random migration of human neutrophils. An optimally stimulatory effect was observed with 10 microM 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 accumulation, and by antagonists of cGMP-dependent protein kinase (G-kinase). These results strongly suggest that the enhancement of random migration by CO is mediated by cGMP and G-kinase. Using hemoglobin, a scavenger of CO, we could show that stimulation of soluble guanylate cyclase over an extended period of time, rather than the observed fast and transient increase in intracellular cGMP levels, is responsible for CO-activated migration. We postulate that CO, like nitric oxide (NO), acts as a biological signal in the immune system.
VanUffelen
B E
BE
Department of Medical Biochemistry, Sylvius Laboratories, Leiden University, The Netherlands.
de Koster
B M
BM
VanSteveninck
J
J
Elferink
J G
JG
D000634:Aminoquinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002248:Carbon Monoxide / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D004336:Drug Antagonism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008751:Methylene Blue / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000634:Aminoquinolines; D002248:Carbon Monoxide; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008751:Methylene Blue