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A STUDY ON MECHANISM OF THE DELAYED CELL IMPAIREMANT OF THE AIRWAY MUCOSA - RELEVANCE OF THE LIPID MEDIATORS TO NITRIC OXIDE AND SUPER OXIDE -

Research Project

Project/Area Number 12671684
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionNihon University

Principal Investigator

HISAMATSU Ken-ichi  NIHON UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (60165107)

Co-Investigator(Kenkyū-buntansha) INOUE Hajime  NIHON UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 講師 (60193603)
YAMAUCHI Yuki  NIHON UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (10267073)
MAKIYAMA Kiyoshi  NIHON UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (00139172)
KAMETANI Ryuichi  NIHON UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (30256862)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordshuman nasal mucosa / delayed mucosal cell impairment / lipid mediator / nitric oxide / superoxide / nitrotyrosine / leukotriene D_4 / platelet activating factor / 鼻アレルギー / 気道粘膜細胞障害 / ロイコトリエンD4 / ECP
Research Abstract

The aim of this project is to clarify nasal mucosal impairment in nasal allergy patients and to get clues to the solution of the mechanisms of lipids mediators induced delayed impairment of airway mucosa.
I. The following substances were measured in the nasal lavage fluids from nasal allergy patients, and urea was also measured in sera and the lavage fluids for conversion in the nasal secretions. Results : Followings showed significant relationships ; 1) alkariphosphatase activity (ALP) and LDH activity (LDH), 2) ECP and LDH, 3) ECP and ALP, 4) NO and nitrotyrosine (NT), 5) NT and ALP, although followings did not show significant relationships, 6) NT and LDH, 7) ECP and NT. These suggested (1) impairment of allergic nasal mucosa, (2) nasal mucosal cell membrane impairment and flux of LDH from cytoplasm, (3) cell membrane impairment by NO and superoxide system, (4) capable difference between fluxes of ALP from cell membrane and ADH from cytoplasm, (5) NO and superoxide protein impairment system is independent from eosinophil granule protein injurious system.
II. LDH, ALP, NO and NT were measured in the medium before and after exposure of 10^<-7> M, 10^<-8> MLTD_4 or PAF to nasal mucosa obtained at a time of surgery. Results : These substances showed tend to increase in progress. (2) Leukotriene receptor antagonist, pranlukast, inhibited LTD_4 induced these increases in the medium. (3) The nasal mucosa exposed to lipid mediators were diffusely stained by anti-NT antibody compared to the control. (4) NT was detected in the culture medium with human bronchial epithelial cells following exposure to LTD_4 or PAF after 24 hours. These data suggest that NT detected in the nasal lavage fluids may be attributable from not only epithelial cells but also other mucosal component cells. For the further investigation of the mechanism of the lipid mediator induced delayed mucosal cell impairment, mRNA level of xanthine oxidase and nitric oxside synthase should be studied.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Hisamatsu K, Nakajima M: "Pranlukast protects leukotriene C_<4-> and D_4-induced epithelial cell impairment of the nasal mucosa in vitro"Life Sciences. 67. 2767-2773 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue H, Ando K, Wakisaka N, et al.: "Effect of nitric oxide synthase inhibitors on vascular hyperpermeability with thermal injury in mice"NITRIC OXIDE. 5. 334-342 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue H, Hisamatsu K, et al.: "Detection of nitrotyrosine and related compounds in biological specimens by competitive enzyme immunoassay"NITRIC OXIDE : Biology and Chemistry. (In print).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hisamatsu K and Nakajima M: "Pranlukast protects leukotriene C_4- and D_4-induced epithelial cell impairment of the nasal mucosa in vitro"Life Sciences. 67. 2767-2773 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue H, Ando K, Wakisaka N, et al.: "Effect of nitric oxide synthase inhibitors on vascular hyperpermeability with thermal injury in mice"NITRIC OXIDE. 5. 334-342 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue H, Hisamatsu K, et al.: "Detection of nitrotyrosine and related compounds in biological specimens by competitive enzyme immunoassay"NITRIC OXIDE : Biology and Chemistry. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hisamatsu K, Nakajima M: "Pranlukast protects leukotriene C_4- and D_4-induced epithelial cell impairment of the nasal mucosa in vitro"Life Sciences. 67. 2767-2773 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue H, Hisamatsu K, et al.: "Rapid and simple determination of histamine-N-methyl transferase activity by high-performance liquid chromatography with UV determination"Mediators of Inflammation. 10. 273-277 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue H, Hisamatsu K, et al.: "Determination of Nitrotyrosine and Related Compounds in Biological Specimens by Competitive Enzyme Immunoassay"NITRIC OXIDE : Biology and Chemistry.

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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