title: Early histopathology of small intestinal discordant xenografts.
abstract: A descriptive study of a new model enabling serial biopsies of ongoing hyperacute rejection of small intestinal discordant xenografts is presented. In a series of guinea-pig-to-Lewis rat small bowel xenotransplants (n=7), aboral free ends of Thierry-Vella loops constructed from the graft were sequentially biopsied at one-minute intervals up to ten minutes post-reperfusion and less frequently thereafter. In a guinea pig-to-guinea pig (n=6) isograft series, biopsy controls for preservation/ischemia-reperfusion injury were obtained. Xenoantibody sequestration in this model was evaluated in a separate series of transplants, utilizing an ELISA assay for rat anti-guinea pig natural antibodies. Pathologic evaluation revealed a unique series of events characterized with microcirculatory failure and thrombosis progressing from the submucosal vasculature to the lumen. Within the system's detection limits, complement deposition and P-selectin expression occurred as early as one minute post-reperfusion, preceding the staining for IgM and IgG. Using rat serum ELISAs, no significant difference in xenoantibody sequestration was detected between the xenograft and isograft groups. The guinea pig-to-rat discordant small bowel xenotransplantation is an efficient small animal model to dissect the very early pathophysiologic events during hyperacute rejection.
authors.affiliation: Department of Surgery, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Yedidag
authors.forename: J P
authors.initials: JP
authors.lastname: Fryer
authors.forename: E
authors.initials: E
authors.lastname: Levi
authors.forename: F C
authors.initials: FC
authors.lastname: Buckingham
authors.forename: D
authors.initials: D
authors.lastname: Ivancic
authors.forename: J
authors.initials: J
authors.lastname: Kraff
authors.forename: C F
authors.initials: CF
authors.lastname: Huang
authors.forename: A W
authors.initials: AW
authors.lastname: Rademaker
authors.forename: D B
authors.initials: DB
authors.lastname: Kaufman
authors.forename: M
authors.initials: M
authors.lastname: Abecassis
authors.forename: F P
authors.initials: FP
authors.lastname: Stuart
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis; D001706:Biopsy; D001792:Blood Platelets / Q000166:cytology; D003170:Complement Pathway, Alternative / Q000502:physiology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D019007:P-Selectin / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000150:complications; D014183:Transplantation, Heterologous / Q000276:immunology / Q000473:pathology*; D014185:Transplantation, Isogeneic / Q000276:immunology
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019007:P-Selectin