title: Alpha1-acid glycoprotein suppresses rat acute inflammatory paw edema through the inhibition of neutrophils activation and prostaglandin E2 generation.
abstract: Alpha(1)-acid glycoprotein (AGP) is an acute phase protein. Whereas the expression of AGP in an inflammatory state is enhanced by inflammatory cytokines including interleukin-1, 6 (IL-1 and IL-6), and tumor necrosis factor-alpha (TNF-alpha), the biological significance of AGP remains unclear. In the current study, the anti-inflammatory effect of AGP on the acute inflammatory state was examined in vivo and in vitro. AGP suppressed carrageenan-, dextran- and kaolin-induced paw edema and vascular permeability in rat. These results suggest that both initial inflammatory mediators (serotonin and histamine) and later inflammatory mediators (prostaglandin and bradykinin) are involved in the anti-inflammatory effects of AGP. In fact, prostaglandin E(2) (PGE(2)) generation in plasma was significantly inhibited by AGP. Moreover, AGP inhibited the migration of neutrophils treated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) through membrane filter. In addition, AGP significantly suppressed superoxide generation from neutrophils that has been treated with fMLP or phorbol 12-myristate 13-acetate. These results imply that the anti-inflammatory effect of AGP may involve the inhibition of neutrophils migration. The data obtained in this study support a scenario in which an increase in AGP concentration in pathological conditions suppresses inflammation reactions induced by autacoids and neutrophils activities and that AGP plays an important role in the maintenance in the body.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Kumamoto, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Nishi
authors.forename: Mari
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tokutomi
authors.forename: Naofumi
authors.initials: N
authors.lastname: Tokutomi
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Nishi
authors.forename: Ayaka
authors.initials: A
authors.lastname: Suenaga
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004487:Edema / Q000188:drug therapy*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009961:Orosomucoid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D009961:Orosomucoid; D015232:Dinoprostone