RESEARCH ON APOPTOTIC CELL DEATH IN THE RAT HINDLIMB ALLOTRANSPLANTATION MODEL OF ACUTE REJECTION

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591896
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Plastic surgery
• Research Institution: TOHOKU UNIVERSITY
• Principal Investigator: IMAI Yoshimichi TOHOKU UNIVERSITY, HOSPITAL, RESEARCH ASSOCIATE, 病院, 助手 (80323012)
• Project Period (FY): 2003 – 2004
• Keywords: RAT HINDLIMB TRANSPLANTATION / ALLOGRAFT / ISOGRAFT / ACUTE REJECTION / APOPTOSIS / DNaseγ / TUNEL METHOD

Research Abstract

ALLOTRANSPLANTATION (FISHER 344 TO LEWIS) AND ISOTRANSPLANTATION (LEWIS TO LEWIS) OF THE RAT LOWER EXTREMITIES WERE PERFORMED. TEMPORAL PROFILES OF DNASEY WERE CONDUCTED BY QUANTITATIVE WESTERN BLOT ANALYSIS AND IMMUNOHISTOCHEMISTRY. ALSO, WE PERFORMED TUNEL TO DETECT APOPTOTIC CELL DEATH IN THE GRAFTS. ANALYSES WERE PERFORMED IMMEDIATELY AFTER REPER-FUSION (DAY 0), AND ON POSTOPERATIVE DAYS (PODS) 1, 3, 7,12 (N = 5 FOR QUANTITATIVE WESTER BLOT ANALYSIS AND N = 5 FOR IMMUNOHISTOCHEMISTRY).
THE EXPRESSION LEVELS OF DNASEY WERE UNIFORMLY AND SIGNIFICANTLY AUGMENTED UNTIL POD 7 IN THE ALLOGRAFTS, COMPARED WITH ISOGRAFTS (P< 0.001). IMMUNOREACTIVITIES TO DNASEY IN KERATINOCYTES, HAIR FOLLICULAR CELLS AND ENDTHELIAL CELLS OF SUBDERMAL VASCULAR PLEXUS WERE ENHANCED IN THE ALLOGRAFTS ON POD 1. ALSO, WE DETECTED APOPTOTIC CELL DEATH IN THE SAME TYPES OF CELLS POSITIVE TO DNASEY IMMUNOHISTOCHEMISTRY.
THESE RESULTS SUGGEST THE POSSIBLE INVOLVEMENT OF APOPTOTIC CELL DEATH IN THE PROCESS OF MHC-COMPATIBLE MINOR-MISMATCH ALLOGRAFT REJECTION. HENCE, MODULATION OF MECHANISMS OF APOPTOSIS MIGHT BE AN IMPORTANT THERAPEUTIC OPTION FOR IMPROVING THE OUTCOME OF MHC-COMPATIBLE MINOR-MISMATCH ALLOGRAFTS.