title: Effects of reactive oxygen and nitrogen metabolites on MCP-1-induced monocyte chemotactic activity in vitro.
abstract: Peroxynitrite, an oxidant generated by the interaction between superoxide and nitric oxide (NO), can nitrate tyrosine residues, resulting in compromised protein function. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that attracts monocytes and has a tyrosine residue critical for function. We hypothesized that peroxynitrite would alter MCP-1 activity. Peroxynitrite attenuated MCP-1-induced monocyte chemotactic activity (MCA) in a dose-dependent manner (P < 0.05) but did not attenuate leukotriene B4 or complement-activated serum MCA. The reducing agents dithionite, deferoxamine, and dithiothreitol reversed the MCA inhibition by peroxynitrite, and exogenous L-tyrosine abrogated the inhibition by peroxynitrite. PAPA-NONOate, an NO donor, or superoxide generated by xanthine and xanthine oxidase did not show an inhibitory effect on MCA induced by MCP-1. The peroxynitrite generator 3-morpholinosydnonimine caused a concentration-dependent inhibition of MCA by MCP-1. Peroxynitrite reduced MCP-1 binding to monocytes and resulted in nitrotyrosine formation. These findings are consistent with nitration of tyrosine by peroxynitrite, with subsequent inhibition of MCP-1 binding to monocytes, and suggest that peroxynitrite may play a role in regulation of MCP-1-induced monocyte chemotaxis.
authors.affiliation: Research Services, Tucson and Overton Brooks Veterans Affairs Medical Centers, and Department of Medicine, University of Arizona, Tucson, Arizona 85723, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sato
authors.forename: K L
authors.initials: KL
authors.lastname: Simpson
authors.forename: M B
authors.initials: MB
authors.lastname: Grisham
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: R A
authors.initials: RA
authors.lastname: Robbins
mesh_terms: D001790:Blood Physiological Phenomena; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D009566:Nitrates / Q000494:pharmacology; D009584:Nitrogen / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019163:Reducing Agents / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D009566:Nitrates; D016877:Oxidants; D017382:Reactive Oxygen Species; D019163:Reducing Agents; D013481:Superoxides; D007975:Leukotriene B4; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D009584:Nitrogen