Molecular Markers and Targeted Therapy of Skin Rejection in Composite Tissue Allotransplantation

被引：63

作者：

Hautz, T. ^{[1
]}

Zelger, B. ^{[2
]}

Grahammer, J. ^{[1
]}

Krapf, C. ^{[1
]}

Amberger, A. ^{[3
]}

Brandacher, G. ^{[1
]}

Landin, L. ^{[4
]}

Mueller, H. ^{[5
]}

Schoen, M. P. ^{[6
]}

Cavadas, P. ^{[4
]}

Lee, A. W. P. ^{[7
]}

Pratschke, J. ^{[1
]}

Margreiter, R. ^{[1
]}

Schneeberger, S. ^{[1
,7
,8
]}

机构：

[1] Innsbruck Med Univ, Ctr Operat Med, Dept Visceral Transplant & Thorac Surg, Innsbruck, Austria

[2] Innsbruck Med Univ, Dept Pathol, Innsbruck, Austria

[3] Innsbruck Med Univ, Tyrolean Canc Res Inst, Innsbruck, Austria

[4] La Fe Univ Hosp, Div Plast & Reconstruct Surg, Valencia, Spain

[5] Innsbruck Med Univ, Dept Dermatol, Innsbruck, Austria

[6] Univ Gottingen, Dept Dermatol, Gottingen, Germany

[7] UPMC, Dept Surg, Div Plast Surg, Pittsburgh, PA USA

[8] VA Healthcare Syst Univ, Dr Div, Dept Surg, Pittsburgh, PA USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2010年 / 10卷 / 05期

关键词：

Adhesion molecules; composite tissue allograft; composite tissue transplantation; hand transplantation; lymphocyte trafficking; rat; rejection; selectin ligand inhibition; skin; topical therapy; FOREARM TRANSPLANTATION; HAND TRANSPLANTATION; ADHESION MOLECULES; FACE ALLOGRAFT; C4D DEPOSITION; INFLAMED SKIN; E-SELECTIN; TRAFFICKING; CLASSIFICATION; MECHANISMS;

D O I：

10.1111/j.1600-6143.2010.03075.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 +/- 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival.

引用

页码：1200 / 1209

页数：10

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