Role of mast cell chymase in allergen-induced biphasic skin reaction.
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.
Tomimori
Yoshiaki
Y
Suntory Biomedical Research Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
Tsuruoka
Nobuo
N
Fukami
Harukazu
H
Saito
Kayo
K
Horikawa
Chika
C
Saito
Masayuki
M
Muto
Tsuyoshi
T
Sugiura
Namino
N
Yamashiro
Kyoko
K
Sumida
Motoo
M
Kakutani
Saki
S
Fukuda
Yoshiaki
Y
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*
D006633:Histamine Antagonists; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D053818:Chymases