Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model

PLoS One

Or Friedman¹  Moshe Ben Hamou¹  Amir Inbal¹  Yakov Krelin¹  Nir Shani¹  Eyal Gur¹  Narin Carmel¹  Ameen Abu Jabal¹  Meirav Sela¹ 

[1] The Plastic Reconstructive Surgery Department, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

关键词: Inflammation;    Immune response;    Transplant rejection;    Transplantation immunology;    Gene expression;    Skin grafting;    Cytokines;    Hematoxylin staining;   

DOI  :  10.1371/journal.pone.0181507

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background Hand and face vascularized composite allotransplantation (VCA) is an evolving and challenging field with great opportunities. During VCA, massive surgical damage is inflicted on both donor and recipient tissues, which may contribute to the high VCA rejection rates. To segregate between the damage-induced and rejection phase of post-VCA responses, we compared responses occurring up to 5 days following syngeneic versus allogeneic vascularized groin flap transplantations, culminating in transplant acceptance or rejection, respectively. Methods The immune response elicited upon transplantation of a syngeneic versus allogeneic vascularized groin flap was compared at Post-operative days 2 or 5 by histology, immunohistochemistry and by broad-scope gene and protein analyses using quantitative real-time PCR and Multiplex respectively. Results Immune cell infiltration began at the donor-recipient interface and paralleled expression of a large group of wound healing-associated genes in both allografts and syngrafts. By day 5 post-transplantation, cell infiltration spread over the entire allograft but remained confined to the wound site in the syngraft. This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and 11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in the induction of the anti-alloantigen adaptive immune response. Conclusions High resemblance between the cues governing VCA and solid organ rejection was observed. Despite this high resemblance we describe also, for the first time, a damage induced inflammatory component in VCA rejection as immune cell infiltration into the graft initiated at the surgical damage site spreading to the entire allograft only at late stage rejection. We speculate that the highly inflammatory setting created by the unique surgical damage during VCA may enhance acute allograft rejection.

【 授权许可】

CC BY