title: Role of mast cell chymase in allergen-induced biphasic skin reaction.
abstract: Intradermal injection of human chymase (EC 3.4.21.39) into the mouse ear elicited an edematous skin reaction in a biphasic manner, with a transient reaction peaking at 1 hr, followed by a delayed response persisting for at least 24hr. The kinetics of this reaction was analogous to the biphasic skin reaction induced by ascaris extract in actively sensitized mice. A similarity between the two dermatitis models was also shown by histological analysis, i.e. accumulation of inflammatory cells was observed exclusively in the later phases of the skin reaction. A chymase inhibitor, SUN-C8077 [3-(3-aminophenylsulfonyl)-7-chloroquinazorine 2,4(1H, 3H)-dione], significantly inhibited both the early- and late-phase responses of the skin reaction induced by ascaris extract. These findings suggest that chymase may play an important role in the allergen-induced biphasic skin reaction. A histamine receptor antagonist, homochlorcyclizine, inhibited the early-phase but not the late-phase of the chymase-induced skin reaction. In addition, human chymase showed chemotactic activity to human polymorphonuclear leukocytes in vitro. Mast cell chymase may participate in the two phases of allergic skin inflammation by two distinct mechanisms, i.e. histamine- and leukocyte-dependent mechanisms, respectively.
authors.affiliation: Suntory Biomedical Research Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tomimori
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuruoka
authors.forename: Harukazu
authors.initials: H
authors.lastname: Fukami
authors.forename: Kayo
authors.initials: K
authors.lastname: Saito
authors.forename: Chika
authors.initials: C
authors.lastname: Horikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saito
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Muto
authors.forename: Namino
authors.initials: N
authors.lastname: Sugiura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamashiro
authors.forename: Motoo
authors.initials: M
authors.lastname: Sumida
authors.forename: Saki
authors.initials: S
authors.lastname: Kakutani
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D002633:Chemotaxis; D053818:Chymases; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006633:Histamine Antagonists / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000494:pharmacology*
chemical_list: D006633:Histamine Antagonists; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D053818:Chymases