Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection.
Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units, respectively) compared to control (6.6 +/- 1.0) (P < 0.05). In histology, the intensity of portal inflammation was significantly decreased (P < 0.05). The amount of T cells expressing activation markers diminished. This is the first demonstration in any prolonged in vivo model that VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection.
Martelius
Timi
T
Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 340, 00029 HUS Helsinki, Finland. timi.martelius@helsinki.fi
Salaspuro
Ville
V
Salmi
Marko
M
Krogerus
Leena
L
Höckerstedt
Krister
K
Jalkanen
Sirpa
S
Lautenschlager
Irmeli
I
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D001707:Biopsy, Needle; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D002465:Cell Movement; D006084:Graft Rejection / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D014184:Transplantation, Homologous
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)