Departmental Bulletin Paper Monoclonal Antibody to Very Late Antigen-4 (VLA-4) Protects Skin Flaps against Ischemia-Reperfusion Injury: An Experimental Study in Rats

KOGA Yasushi :筆頭著者:責任著者  ,  TOSA Yasuyoshi  ,  TOSA Nozomi  ,  MANDRANO Nirina Adrien Jean Vivier  ,  SATO Nobuhiro  ,  YOSHIMOTO Shinya

29 ( 4 )  , pp.365 - 372 , 2017-12 , Showa University Society
In recent years, various adhesion molecules have been discovered. Very late antigen-4 (VLA-4), an adhesion molecule belonging to the integrin family, plays an important role in lymphocyte migration and infiltration into sites of inflammation. In the present study, we investigated whether administration of anti-VLA-4 monoclonal antibody (mAb) reduces inflammation in ischemia-reperfusion injury using a skin flap model in Sprague-Dawley rats. A superficial epigastric arteriovenous pedicle flap, sized 45×30mm, was elevated in the right inguinal area. The vessel was clamped to induce ischemia and the clamp was removed after 9hours. Fifteen minutes prior to clamp release, the rats were administered anti-VLA-4 mAb (0.2mg/kg i.v., n=10) or saline (n=10). At the same time, a sham group (n=5) was established with a similar operation but the vessel was only clamped to induce ischemia for 5minutes. Anti-VLA-4 mAb significantly improved the survival area of the skin flap to 92.4% (median), when compared to 12.5% (median) in the control group. Severe inflammatory cell infiltration and edema was consistently observed in the skin flaps of the control group, while anti-VLA-4 reduced these parameters to a level similar to the sham group. These results indicate that anti-VLA-4 mAb may be used as an anti-inflammation agent, however the underlying mechanism still remains to be elucidated.

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