A1 Refereed original research article in a scientific journal
Inhibition of semicarbazide-sensitive amine oxidases decreases lymphocyte infiltration in the early phases of rat liver allograft rejection
Authors: Martelius T, Salmi M, Krogerus L, Loginov R, Schoultz M, Karikoski M, Miiluniemi M, Soots A, Hockerstedt K, Jalkanen S, Lautenschlager I
Publisher: BIOLIFE SAS
Publishing place: Silva Marina
Publication year: 2008
Journal: International Journal of Immunopathology and Pharmacology
Journal name in source: INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
Journal acronym: Int J Immunopathol Pharmacol
Volume: 21
Issue: 4
First page : 911
Last page: 920
Number of pages: 10
ISSN: 0394-6320
DOI: https://doi.org/10.1177/039463200802100415(external)
Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation in vitro and in vivo. VAP-1 is also an ectoenzyme with semicarbazide-sensitive amine oxidase (SSAO) activity. In this study we investigated whether inhibition of SSAO influences the inflammatory infiltration in acute rat liver allograft rejection. BN recipients of DA liver allografts were treated with 50 mg/kg/d semicarbazide, an inhibitor of SSAO, or similar volumes of saline. 10 rats/ group were followed for graft survival, and 10 rats/group were sacrificed on day 7 post-transplantation for histology and T-lymphocyte isolation. The area percentage of portal inflammatory infiltrates in the grafts was assessed from digital photomicrographs. The proportion of CD4-, CD8- and IL2-receptor positive lymphocytes in the graft was quantified with flow cytometry. On day 7, semicarbazide treatment significantly decreased the inflammatory infiltrate area in the grafts. CD4-, CD8- and IL2-receptor positive cells were equally affected. However, animal survival was not affected. Blockade of the enzymatic activity of VAP-1 has a significant effect on lymphocyte infiltration early in acute liver rejection. Later, activation of other adhesion pathways can by-pass the blockade caused by VAP-inhibition.