title: Resident macrophages are involved in intestinal transplantation-associated inflammation and motoric dysfunction of the graft muscularis.
abstract: Gut manipulation and ischemia/reperfusion evoke an inflammatory response within the intestinal muscularis that contributes to dysmotility. We hypothesize that resident macrophages play a key role in initiating the inflammatory cascade. Isogenic small bowel transplantation was performed in Lewis rats. The impact of recovery of organs on muscularis inflammation was investigated by comparing cold whole-body perfusion after versus prior to recovery. The role of macrophages was investigated by transplantation of macrophage-depleted gut. Leukocytes were counted using muscularis whole mounts. Mediator expression was determined by real-time RT-PCR. Contractility was assessed in a standard organ bath. Both organ recovery and ischemia/reperfusion induced leukocyte recruitment and a significant upregulation in IL-6, MCP-1, ICAM-1 and iNOS mRNAs. Although organ recovery in cold ischemia prevented early gene expression, peak expression was not changed by modification of the recovery technique. Compared to controls, transplanted animals showed a 65% decrease in smooth muscle contractility. In contrast, transplanted macrophage-depleted isografts exhibited significant less leukocyte infiltration and only a 19% decrease in contractile activity. In summary, intestinal manipulation during recovery of organs initiates a functionally relevant inflammatory response within the intestinal muscularis that is massively intensified by the ischemia reperfusion injury. Resident muscularis macrophages participate in initiating this inflammatory response.
authors.affiliation: Department of Surgery, Universitätsklinikum Bonn, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Schaefer
authors.forename: K
authors.initials: K
authors.lastname: Tahara
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Wehner
authors.forename: J C
authors.initials: JC
authors.lastname: Kalff
authors.forename: K
authors.initials: K
authors.lastname: Abu-Elmagd
authors.forename: A
authors.initials: A
authors.lastname: Hirner
authors.forename: A
authors.initials: A
authors.lastname: Türler
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000502:physiology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D019737:Transplants / Q000009:adverse effects*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D015850:Interleukin-6; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II