title: Role of resident macrophages in the immunologic response and smooth muscle dysfunction during acute allograft rejection after intestinal transplantation.
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.
authors.affiliation: Department of Surgery, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany. nico.schaefer@ukb.uni-bonn.de
authors.forename: Nico
authors.initials: N
authors.lastname: Schaefer
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tahara
authors.forename: Martin
authors.initials: M
authors.lastname: von Websky
authors.forename: Sven
authors.initials: S
authors.lastname: Wehner
authors.forename: Thomas
authors.initials: T
authors.lastname: Pech
authors.forename: Rene
authors.initials: R
authors.lastname: Tolba
authors.forename: Kareem
authors.initials: K
authors.lastname: Abu-Elmagd
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Kalff
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirner
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D005769:Gastrointestinal Motility; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D007583:Jejunum / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D016753:Interleukin-10