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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:18.)
© 2008 American Heart Association, Inc.

Brief Reviews

VAP-1 and CD73, Endothelial Cell Surface Enzymes in Leukocyte Extravasation

Sirpa Jalkanen; Marko Salmi

From the MediCity Research Laboratory, and the Department of Microbiology and Immunology, University of Turku, and the Department of Bacterial and Inflammatory Diseases, National Public Health Institute, Turku, Finland.

Correspondence to Sirpa Jalkanen, MediCity Research Laboratory, Tykistökatu 6A, 20520 Turku, Finland. E-mail sirpa.jalkanen{at}utu.fi

Series Editor: Dietmar Vestweber
Vascular Adhesion Molecules
ATVB In Focus

Previous Brief Reviews in this Series:

•van Buul JD, Kanters E, and Hordijk PL. Endothelial signaling by Ig-like cell adhesion molecules. Arterioscler Thromb Vasc Biol. 2007;27:1870–1876.
•Bradfield PF, Nourshargh S, Aurrand-Lions M, Imhof BA. JAM family and related proteins in leukocyte migration. Arterioscler Thromb Vasc Biol. 2007;27:2104–2112.
•Galkina E and Ley K. Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27: 2292–2301.

Leukocyte extravasation from the blood into tissues is crucial for normal immune surveillance and in inflammation. Traditionally molecules belonging to selectin, chemokine, integrin, and immunoglobulin super families are thought to mediate the multiple adhesive and activation events needed for a successful emigration cascade. Recently, emerging evidence suggests that enzymes expressed on the surface of endothelial cells and leukocytes also contribute to the leukocyte extravasation cascade. Here we briefly review the role of vascular adhesion protein-1 (VAP-1) and CD73, 2 cell surface enzymes, in leukocyte migration form the blood into the tissues. Importantly, specific enzyme inhibitors, gene-deficient mice, and recombinant enzymes have recently unambiguously shown that the catalytic activity of these enzymes regulates the leukocyte traffic. The concept of enzymatic regulation of leukocyte extravasation provides new insight into the multi-step adhesion cascade and opens new possibilities for inhibiting inappropriate inflammatory reaction through the use of small molecule enzyme inhibitors.

Leukocyte extravasation from the blood into tissues is crucial for normal immune surveillance and in inflammation. Emerging evidence suggests that enzymes expressed on the surface of endothelial cells and leukocytes contribute to the leukocyte extravasation cascade. They also provide new possibilities to inhibit inappropriate inflammations.

Key Words: leukocyte traffic • migration • endothelium • inflammation • ectoenzymes