気管支喘息における接着分子 (VLA-4) の重要性 : 薬効評価モデルとしての可能性の検討 Role of Adhesion Molecules (VLA-4) in the Asthmatic Response to Allergens

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Brown-Norway (BN) ラット喘息モデルを用いて抗原暴露前後の very late antigen-4 (VLA-4) 陽性細胞の肺内動態を免疫組織化学的手法を用いて検討した. また抗VLA-4抗体投与の遅発型喘息反応 (late asthmatic response, LAR) におよぼす影響を呼吸抵抗 (Zrs) の変化と肺内浸潤好酸球数について検討し, 新しく抗アレルギー薬として開発されたTYB-2285 (3,5bis (acetoxyacetylamino)-4-chloro-benzonitrile) の喘息反応に対する効果も評価した. LAR時におけるZrs, 好酸球数, VLA-4陽性細胞数は非暴露感作群に比較して有意に増加し, 抗VLA-4抗体投与によりZrs, 好酸球数の増加は抑制された. またTYB-2285投与によりZrs, 好酸球数, VLA-4陽性細胞数の増加はともに抑制された. 以上の結果より, VLA-4/VCAM-1経路の喘息病態における重要な役割が示唆された. またVLA-4陽性細胞浸潤は, 呼吸抵抗, 好酸球浸潤とともに喘息反応の重要な指標であると考えられた.

We evaluated the role of very late antigen-4 (VLA-4) in asthmatic responses. Brown-Norway rats were sensitized with ovalbumin and then challenged with ovalbumin. Respiratory impedance, and the influx of eosinophils and of VLA-4-positive cells were measured. Eosinophils were stained with Giemsa's solution and VLA-4-positive cells were detected by an immunocytochemical method with a monoclonal antibody against rat VLA-4 (MRα4-1). The numbers of eosinophils and of VLA-4-positive cells in sections of lung tissue from the rats were counted. The effect of MRα4-1 and of a new anti-allergic drug, TYB-2285, on late asthmatic responses was also studied. Respiratory impedance had increased in all the rats by 6-7 hours after the challenge, which indicated that these animals had a late asthmatic response. These rats had more eosinophils and more VLA-4-positive cells than did sensitized animals that were not challenged. The rats given MRα4-1 had significantly smaller increases in respiratory impedance and less eosinophil influx than did those given only phosphate-buffered saline. The rats given TYB-2285 had significantly smaller increases in impedance and less influx of eosinophils and of VLA-4-positive cells. These results show that infiltration of eosinophils and of VLA-4-positive cells corresponds closely with the late asthmatic response, and they suggest that the VLA-4/VCAM-1 pathway plays an important role in this response. These data also suggest that the infiltration of VLA-4-positive cells can be used to evaluate the effect of anti-allergic drugs on the late asthmatic response.

収録刊行物

  • 日本胸部疾患学会雑誌 = The Japanese journal of thoracic diseases

    日本胸部疾患学会雑誌 = The Japanese journal of thoracic diseases 33(11), 1240-1249, 1995-11-25

    The Japanese Respiratory Society

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各種コード

  • NII論文ID(NAID)
    10008108771
  • NII書誌ID(NCID)
    AN00187758
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    03011542
  • データ提供元
    CJP書誌  J-STAGE 
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