Influence of macrophage depletion on bacterial translocation and rejection in small bowel transplantation

Jonathan Fryer*, David Grant, Jifu Jiang, Peter Metrakos, Necdet Ozcay, Carol Ford, Bertha Garcia, Ron Behme, Robert Zhong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Rejection and sepsis can be intimately related following small bowel transplantation when rejection compromises normal intestinal barrier mechanisms and bacterial translocation results. Macrophages play a role in controlling the egress of intestinal luminal bacteria-and they have also been implicated in allograft rejection. In this study, the role of macrophages in rejection and bacterial translocation was evaluated by depleting macrophages in donors and/or recipients of rat small bowel allografts with injection of liposome-encapsulated dichloromethylene diphosphonate (CL2MDP). In preliminary studies, we demonstrated that a single intraperitoneal injection of liposome-encapsulated CL2MDP (350 mg/kg) depleted ED2-positive macrophages by >90% in the liver mesenteric lymph nodes and proximal and distal small bowel, and by approximately 50% in the spleen. ED1-positive macrophages were depleted by >90% in the liver and by approximately 50% at the other sites. ED3-positive macrophages were completely depleted. Dendritic cells were >90% depleted in the spleen and roesenteric lymph nodes, but were not depleted in the small bowel. Macrophage depletion in the donor resulted in increased translocation of bacteria to the peritoneal cavity (P=0.03) if recipient macrophages were present. With histopathologic analysis, a significantly milder rejection with less arteritis was seen in the allografts of the recipient macrophage-depleted group compared with nondepleted controls (P=0.045). This suggests that recipient macrophages play an important role in rejection. With macrophage depletion in both the donor and the recipient, graft survival was prolonged significantly (13.2±1.9 days) compared with non-macrophage-depleted controls (9.2±1.3 days) (P=0.003). These studies suggest that strategies targeting recipient macrophages may be useful in controlling small bowel allograft rejection without increasing bacterial translocation.

Original languageEnglish (US)
Pages (from-to)553-559
Number of pages7
JournalTransplantation
Volume62
Issue number5
DOIs
StatePublished - Sep 15 1996

ASJC Scopus subject areas

  • Transplantation

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