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  • Title: Role of resident macrophages in the immunologic response and smooth muscle dysfunction during acute allograft rejection after intestinal transplantation.
    Author: Schaefer N, Tahara K, von Websky M, Wehner S, Pech T, Tolba R, Abu-Elmagd K, Kalff JC, Hirner A, Türler A.
    Journal: Transpl Int; 2008 Aug; 21(8):778-91. PubMed ID: 18492123.
    Abstract:
    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, TNFalpha, IFNgamma, 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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