Induction and function of vascular adhesion protein-1 at sites of inflammation.

M Salmi,S Jalkanen,K Kalimo

doi:10.1084/jem.178.6.2255

Abstract

Emigration of leukocytes from the blood into the tissues is critical in controlling lymphocyte patrolling in different lymphatic organs and in leukocyte accumulation at sites of inflammation. During the first stage of the extravasation process, leukocytes bind to the endothelial lining of vessels. At the molecular level, several adhesion molecules on leukocytes and endothelial cells function as receptor-ligand pairs in mediating this dynamic interaction. Recently, we have identified a novel human endothelial cell molecule, vascular adhesion protein 1 (VAP-1), that mediates lymphocyte binding (Salmi, M., and S. Jalkanen. 1992. Science [Wash. DC] 257:1407). VAP-1 was initially characterized by mAb 1B2 which inhibits lymphocyte adhesion to high endothelial venules (HEV) and to purified VAP-1 protein. Here we report the location and function of VAP-1 in normal and inflamed tissues in humans. VAP-1 is abundant in HEV of lymphatic organs belonging to the peripheral lymph node system, but considerably less is expressed in vessels of mucosa-associated lymphatic tissues. A subset of venules in most normal nonlymphatic tissues like skin, brain, kidney, liver, and heart is also VAP-1 positive. In addition to vessels, VAP-1 is distributed on a few other cell types, most notably in dendritic-like cells of germinal centers. At sites of inflammation, such as in inflammatory bowel diseases and chronic dermatoses, expression of VAP-1 is clearly increased. The induced VAP-1 is functional, since mAb 1B2 inhibits lymphocyte binding to inflamed lamina propria venules by approximately 60%. Thus VAP-1 is an endothelial adhesion molecule that under normal conditions is expressed mainly in HEV of lymphatic tissues. However, expression of functional VAP-1 in vivo is upregulated during an inflammatory reaction at other sites as well. Inducibility of VAP-1 suggests that it may play a significant role, not only in recirculation of lymphocytes, but also in controlling entry of leukocytes into sites of inflammation.

Highlights

We have recently characterized a novel endothelial cell adhesion antigen called vascular adhesion protein 1 (VAP-1) that mediates lymphocyte binding to high endothelial venules (HEV) in peripheral lymph nodes, tonsils, and inflamed synovia in humans [17]
The most prominent staining was seen in endothelial cells of HEV through which most lymphocyte trafficking in these organs takes place
In large-sized vessels, VAP-1 was confined to smooth muscle cells of the vessel wall rather than to the endothelial cell layer

Summary

Emigration of leukocytes from the blood into the tissues is critical in controlling lymphocyte patrolling in different lymphatic organs and in leukocyte accumulation at sites ofinflammation. We have identified a novel human endothelial cell molecule, vascular adhesion protein i (VAP-1), that mediates lymphocyte binding The efficiency ofimmune defense is largely dependent on the ability ofleukocytes to continuously survey different anatomical locations in the body and to rapidly accumulate at sites of antigenic insult To perform this function, leukocytes must first bind to vascular endothelium and transmigrate between the endothelial cells into the underlying tissue. We have recently characterized a novel endothelial cell adhesion antigen called vascular adhesion protein 1 (VAP-1) that mediates lymphocyte binding to high endothelial venules (HEV) in peripheral lymph nodes, tonsils, and inflamed synovia in humans [17]. In the present study we have examined the distribution of VAP-1 in several normal and inflamed organs and tissues in humans and its function in inflammation

Materials and Methods

Large arteries and veins Endothelial cells of intima Media Adventitia

Results and Discussion

Lamina propria venules mAb