Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear.
To investigate the involvement of protease-activated receptor-2 (PAR-2) in allergic dermatitis, we generated PAR-2-deficient (PAR-2(-/-)) mice. Ear thickness, contact hypersensitivity (CH) induced by topical application of picryl chloride (PC) or oxazolone (Ox) after sensitization, and vascular permeability after ear passive cutaneous anaphylaxis (PCA) were compared between wild-type (WT) and PAR-2(-/-) mice. Ear thickness was almost the same in untreated WT and PAR-2(-/-) mice. Topical application of PC or Ox thickened the ears at 6, 24 and 48 h after challenge with a peak at 24 h in WT mice. In PAR-2(-/-) mice, the ear swelling induced by both PC and Ox was suppressed at every time point, and significant inhibition was found at 24 h in PC-induced CH and at 24 and 48 h in Ox-induced CH. Histopathological observation of the ears at 24 h after challenge revealed that PC- or Ox-induced ear edema and infiltration of inflammatory cells in WT mice were greatly attenuated in PAR-2(-/-) mice. The vascular permeability in the ears after PCA was not different between WT and PAR-2(-/-) mice. These results strongly suggest that PAR-2 plays a crucial role in type IV allergic dermatitis but not in type I allergic dermatitis.
Kawagoe
Junichi
J
Tokyo Research Laboratories, Pharmaceutical Division, Kowa Company Ltd., Higashimurayama, Japan. jkawagoe@kowa.co.jp
Takizawa
Toshiaki
T
Matsumoto
Jiro
J
Tamiya
Masaki
M
Meek
Stephen E
SE
Smith
Andrew J H
AJ
Hunter
Gary D
GD
Plevin
Robin
R
Saito
Naohiro
N
Kanke
Toru
T
Fujii
Mikio
M
Wada
Yasushi
Y
D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004423:Ear / Q000473:pathology*; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008853:Microscopy; D010081:Oxazolone / Q000009:adverse effects; D010853:Picryl Chloride / Q000009:adverse effects; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000172:deficiency* / Q000235:genetics; D013194:Staining and Labeling; D013997:Time Factors
D000276:Adjuvants, Immunologic; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D010081:Oxazolone; D010853:Picryl Chloride