title: Protection of plasminogen activator inhibitor-1-deficient mice from nasal allergy.
abstract: This study was performed to clarify the relationship between fibrinolytic components and the pathology of allergy, particularly that during the development of nasal allergy and nasal tissue changes. Intranasal OVA challenge after sensitization by i.p. administration of OVA induced a higher level of excess subepithelial collagen deposition in wild-type (WT) C57BL/6J mice than in plasminogen activator inhibitor (PAI)-1-deficient (PAI-1(-/-)) mice. The excess PAI-1 induction in the nasal mucosa and higher level of active PAI-1 in the nasal lavage fluid of WT-OVA mice compared with those in WT-control mice suggested that the decrease of proteolytic activity inhibits the removal of subepithelial collagen. The frequency of sneezing, nasal rubbing, nasal hyperresponsiveness, production of specific IgG1 and IgE in the serum, and production of IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-1(-/-) mice, these reactions were absent, and specific IgG2a in serum and IFN-gamma in splenocyte culture medium increased significantly. Histopathologically, there were marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-1(-/-) mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-1(-/-) mice was down-regulated, and the immune response shifted from Th2-dominant reaction to a Th1-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in immune response.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, and Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, International University of Health and Welfare Hospital, Tochigi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sejima
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Teruko
authors.initials: T
authors.lastname: Sugo
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ueshima
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005342:Fibrinolysis / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000276:immunology; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen