Vascular adhesion protein-1 is involved in both acute and chronic inflammation in the mouse.
Vascular adhesion protein-1 (VAP-1) is an endothelial molecule that possesses both adhesive and enzymatic properties in vitro. So far, however, elucidation of its in vivo function has suffered from the lack of function-blocking reagents that are suitable for use in animal models. In this work we produced monoclonal antibodies against murine VAP-1 and characterized them using in vitro binding assays. We then examined whether the antibodies could prevent leukocyte migration in in vivo inflammation models, including two acute models (peritonitis induced with proteose peptone and interleukin-1 and air pouch inflammation enhanced by CCL21) and one chronic model (autoimmune diabetes in nonobese diabetic mice). Antibodies 7-88 and 7-106 inhibited migration of granulocytes and monocytes in both acute models of inflammation. Strikingly, antibody 7-88 significantly prevented diabetes in a subset of nonobese diabetic mice. The results show for the first time that in mouse models of inflammation, VAP-1 mediates leukocyte trafficking to sites of inflammation and thus is a potential target for anti-inflammatory therapies.
Merinen
Marika
M
MediCity Research Laboratory, University of Turku and National Public Health Institute, 20520 Turku, Finland.
Irjala
Heikki
H
Salmi
Marko
M
Jaakkola
Ilkka
I
Hänninen
Arno
A
Jalkanen
Sirpa
S
D000208:Acute Disease; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology; D007150:Immunohistochemistry; D007249:Inflammation; D019041:L-Selectin / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009000:Monocytes / Q000166:cytology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; C515478:CCL21 protein, human; C515479:Ccl21c protein, mouse; D015815:Cell Adhesion Molecules; D054421:Chemokine CCL21; D019742:Chemokines, CC; D019041:L-Selectin; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)
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