It is crucial that lymphocytes patrol the body against foreign intruders and that

leukocytes invade inflamed tissues to ameliorate the infection or injury. The adhesion

molecules in leukocytes and endothelial cells play an essential role in the immune

response by directing the traffic of leukocytes. However, the same molecules that

guide leukocyte traffic under physiological conditions are also involved in pathological

situations, when an overly excessive or harmful inflammatory response leads to tissue

destruction and organ dysfunction or tumor growth.



Vascular adhesion protein-1 (VAP-1) and Common lymphatic endothelial and

vascular endothelial receptor-1 (CLEVER-1) are endothelial molecules that participate

in the adhesion of leukocytes to the endothelia. This study was designed to elucidate,

using different inflammation models, the role of VAP-1 and CLEVER-1 in leukocyte

migration to the inflamed tissue, and to evaluate the use of antibodies against these

molecules as an anti-adhesive therapy. Also, the role of CLEVER-1 during

tumorigenesis was studied.



Blocking the function of VAP-1 with antibodies significantly decreased the

accumulation of leukocytes in the inflamed tissue. Targeting CLEVER-1 prevented

cell migration via lymphatic vessels, as well as leukocyte traffic during inflammation.

Following the anti-CLEVER-1 antibody treatment the number of immune regulating

leukocytes in tumors was reduced, which led to a decrease in tumor growth. However,

the normal immune response towards immunization or bacterial infection was not

compromised. Thus, VAP-1 and CLEVER-1 are both potential targets for anti-inflammatory therapies for preventing the harmful accumulation of leukocytes in

inflamed areas. Targeting CLEVER-1 may also inhibit tumor growth by reducing

immunosuppressive leukocytes in tumors.