モルモット実験喘息モデルにおける遅発型反応と気道過敏性亢進に及ぼす WEB2086 の影響  [in Japanese] INVOLVEMENT OF PLATELET ACTIVATING FACTOR (PAF) IN OVALBUMIN ANTIGEN-INDUCED LATE ASTHMATIC RESPONS AND INCREASE OF AIRWAY HYPERRESPONSIVENESS IN A GUINEA PIG EXPERIMENTAL MODEL OF ASTHMA  [in Japanese]

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Author(s)

    • 有馬 雅史 Arima Masafumi
    • 獨協医科大学病院アレルギー内科 Department of Medicine and Clinical Immunolog, Dokkyo University School of Medicine
    • 湯川 瀧雄 Yukawa Tatsuo
    • 獨協医科大学病院アレルギー内科 Department of Medicine and Clinical Immunolog, Dokkyo University School of Medicine
    • 相良 博典 Sagara Hironori
    • 獨協医科大学病院アレルギー内科 Department of Medicine and Clinical Immunolog, Dokkyo University School of Medicine
    • 牧野 荘平 Makino Sohei
    • 獨協医科大学病院アレルギー内科 Department of Medicine and Clinical Immunolog, Dokkyo University School of Medicine

Abstract

我々は, すでに卵白アルブミン (OA) 反復吸入能動感作モルモットで抗原曝露後, 50%以上の動物に遅発型発作 (LAR) の出現と, さらに24時間から5日後に気道反応性の亢進が認められることを報告している. 今回, 血小板活性化因子 (PAF) の関与を検討する目的で, 特異的 PAF 桔抗薬である WEB2086 の影響をこれらのモデルを用いて検討した. OAの反復吸入曝露によって感作したモルモットの呼吸低抗は, oscillation 法によって行い, 気道過敏性は, histamine の aerozol 吸入にて呼吸抵抗が baseline の200%に増加する濃度 (PC_<200>Hist.) を以って評価した. OA 10mg/ml を5分間, 感作モルモットに吸入曝露し, 曝露の30分前および3時間後に投与した WEB2086 (3mg/kg×2, i.v.)は, 曝露24時間と5日後における気道過敏性の亢進を有意に抑制した. また, diphenhydramine hydrochloride (60mg/kg, i.p.) を15分前に処置した感作モルモットに OA の20mg/ml を10分間吸入曝露させた場合の即時型の呼吸抵抗の亢進 (IAR) およびその後の LAR において, 曝露30分前および3時間後の WEB2086 (3mg/kg×2, i.v.) の投与は, IAR には影響を及ぼさなかったが, LAR の出現を明らかに抑制した. 以上より気管支喘息患者の LAR 及び気道過敏性の亢進の発現には, PAF の関与が示唆された.

Platelet activating factor, a potent chemical mediator, has been implicated in the pathogenesis of asthma in terms of inflammatory cell recruitment and activation. We have recently demonstrated that repeated antigen (ovalbumin; OA) exposure by inhalation to guinea pigs results in a development of late asthmatic response (LAR) in more than 50% of the animals and significant increase in airway hyperresponsiveness (AH). We have studied the effect of WEB 2086, a specific PAF receptor-antagonist, on this model. Respiratoly resistance (Res) of guinea pigs was measured by a oscillation technique and AH was evaluated by the provocative concentration of aerosols of histamine causing 200% increase of Rrs over the baseline Rrs (PC_<200> Hist). Four out of 5 actively sensitized and diphenhydramine-pretreated animals developed LAR 3 to 9 hr after allergen (20 mg/ml OA, 10 min inhalation)-induced immediate bronchoconstriction (LAR). Treatment with WEB 2086 (3 mg/kg intravenously) 30 min before and 3 hr after the exposure suppressed LAR clearly without affecting the IAR. Significant increase in AH from 2.80±0.03 to 2.51±0.01 and 2.60±0.08 (p < 0.05, n=8) of PC_<200> Hist (mg/ml, log) was observed 24 hr and 5 day after the OA exposure, respectively. The WEB 2086 treatment also prevented the increase of AH after the OA exposure (PC_<200> Hist; 2.82±0.09 before the challenge 2.80±0.07 and 2.75±0.09 24hr and 5 days after, respectively. n=8). Administration of WEB 2086 did not affect baseline Rrs and PC_<200> Hist in normal guinea pigs without any antigen challenge. We conclude that WEB 2086 is capable of preventing the development of LAR and increase in AH, and thus PAF may play an important causal role in LAR and increased AH observed in asthma.

Journal

  • Japanese Journal of Allergology

    Japanese Journal of Allergology 40(2), 141-146, 1991

    Japanese Society of Allergology

Cited by:  2

Codes

  • NII Article ID (NAID)
    110002416591
  • NII NACSIS-CAT ID (NCID)
    AN00012583
  • Text Lang
    JPN
  • Article Type
    Journal Article
  • ISSN
    0021-4884
  • Data Source
    CJPref  NII-ELS  J-STAGE 
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