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Role of resident macrophages in the immunologic response and smooth muscle dysfunction during acute allograft rejection after intestinal transplantation

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Resident muscularis macrophages initiate an inflammatory cascade during ischemia/reperfusion that is associated with dysmotility and the activation of immunologic processes. We hypothesized that these muscularis macrophages may also play a potential immunologic role for acute allograft rejection in intestinal transplantation. Orthotopic SBTx (BN-Lew) was performed without immunosuppression. Animals were sacrificed 7 days after SBTx. The role of resident macrophages was evaluated by transplantation of macrophage-depleted and gadolinium chloride-treated gut. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by Real-Time-RT-PCR. Apoptosis was evaluated by TUNEL. Smooth muscle contractility was assessed in a standard organ bath. In comparison to vehicle-treated grafts, macrophage-depleted grafts exhibited significantly lower mediator mRNA peak expression (IL-6, IL-2, IL-10, MCP-1, iNOS, TNFα, IFNγ, FasL), leukocyte infiltrates (ED1- and ED2 positive monocytes and macrophages, neutrophils, CD4+ and CD8+ lymphocytes), apoptosis rates and an improved histologic rejection grading. Vehicle-treated grafts showed a 77% decrease in smooth muscle contractility compared to naïve controls, while macrophage-depleted gut exhibited only a 51% decrease in contractile activity. Transplantation of macrophage-depleted gut attenuates the functionally relevant molecular and cellular immunologic response within the graft muscularis in acute allograft rejection. Resident macrophages participate in initiating these processes.
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Keywords: acute allograft rejection; inflammation; intestinal muscularis; intestinal transplantation; resident macrophages; smooth muscle function

Document Type: Research Article

Affiliations: 1:  Department of Surgery, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany 2:  House of Experimental Therapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany 3:  Division of Intestinal Transplantation, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA

Publication date: 2008-08-01

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