Abstract |
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.
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Authors | Marika Merinen, Heikki Irjala, Marko Salmi, Ilkka Jaakkola, Arno Hänninen, Sirpa Jalkanen |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 166
Issue 3
Pg. 793-800
(Mar 2005)
ISSN: 0002-9440 [Print] United States |
PMID | 15743791
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Antibodies, Monoclonal
- CCL21 protein, human
- Ccl21c protein, mouse
- Cell Adhesion Molecules
- Chemokine CCL21
- Chemokines, CC
- L-Selectin
- AOC3 protein, human
- Amine Oxidase (Copper-Containing)
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Topics |
- Acute Disease
- Amine Oxidase (Copper-Containing)
(metabolism, physiology)
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Antibodies, Monoclonal
(chemistry, metabolism)
- Cell Adhesion
- Cell Adhesion Molecules
(metabolism, physiology)
- Cell Movement
- Chemokine CCL21
- Chemokines, CC
(metabolism)
- Chronic Disease
- Diabetes Mellitus, Experimental
- Female
- Flow Cytometry
- Granulocytes
(cytology)
- Immunohistochemistry
- Inflammation
- L-Selectin
(metabolism)
- Leukocytes
(cytology, metabolism)
- Lymphocytes
(cytology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred NOD
- Monocytes
(cytology)
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