title: Nitric oxide induces chemotaxis of neutrophil-like HL-60 cells and translocation of cofilin to plasma membranes.
abstract: Nitric oxide (NO) plays various important roles in the physiological system. With regard to chemotaxis of neutrophils, there are reports that endogenous NO is a mediator of chemotaxis, and others that exogenous NO inhibits chemotaxis. It is also reported that NO itself expressed chemotactic activity. On the other hand, we have recently proposed the importance of cofilin, an actin-binding phosphoprotein, in phagocyte functions through dephosphorylation and translocation to the plasma membrane regions. Because chemotaxis is a phenomenon of dynamic cell movement, cofilin, a regulator of the cytoskeletal system, may be involved in its mechanisms. To clarify further the effect of NO on functions of leukocytes and to examine the effect of NO on cofilin, we investigated the chemotaxis of neutrophil-like HL-60 cells induced by NO, as well as the influence of NO on the phosphorylation and intracellular distribution of cofilin. Two NO donors, 3-[2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino]-1-propanamin e (NOC5) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to cause chemotaxis, and, 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO), a NO-specific scavenger, inhibited the chemotaxis induced by NO-donors, suggesting that NO itself released from the NO donors has chemotactic activity. LY-83583 and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), inhibitors of soluble guanylate cyclase, inhibited the chemotaxis to NO donors, which implies that soluble guanylate cyclase is involved in the signaling pathway of this NO action. We also found that NO caused translocation of cofilin to the cell periphery, though dephosphorylation of cofilin was not detected. These results demonstrate that NO has chemotactic activity for neutrophils and caused the translocation of cofilin to the plasma membrane regions without its dephosphorylation.
authors.affiliation: Division of Xenobiotic Metabolism and Disposition, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagayaku, 158-8501, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Adachi
authors.forename: S
authors.initials: S
authors.lastname: Matsui
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
authors.forename: K
authors.initials: K
authors.lastname: Nagaishi
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Kasahara
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D051339:Actin Depolymerizing Factors; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D018922:HL-60 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation
chemical_list: D051339:Actin Depolymerizing Factors; D008840:Microfilament Proteins; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006162:Guanylate Cyclase; D010396:Penicillamine