Leukocyte integrins and beta2-integrins in particular play a crucial role in mediating leukocyte-endothelial interactions and thereby leukocyte recruitment. Leukocyte integrins are thereby important targets to therapeutically interfere with leukocyte recruitment in inflammatory and autoimmune diseases. (a) We have recently identified that developmentally regulated endothelial locus-1 (Del-1) is an endogenous inhibitor of leukocyte recruitment. Del-1 is produced and secreted by endothelial cells. Del-1 expression is found in the lung and in the immunoprivileged tissues brain and eye. We identified that endothelial-derived Del-1 acts to inhibit beta2-integrin-dependent leukocyte adhesion to the endothelium and thereby leukocyte recruitment. Thus, Del-1 is an endogenous anti-inflammatory factor. Del-1-deficient mice displayed higher levels of inflammatory cell recruitment. Since Del-1 expression is high in the brain and eye, the role of Del-1 is currently evaluated in inflammatory and autoimmune processes of these organs. (b) Blood platelets may be involved in the process of leukocyte recruitment. In particular, blood platelets may adhere to the activated endothelium and form a bridge that promotes the arrest of inflammatory cells such as monocytes. The interactions of the leukocyte beta2-integrin Mac-1 with glycoprotein Ib or other adhesion molecules on platelets are important in this process. I.e. platelets can contribute significantly to inflammatory cell recruitment. We are currently investigating the role of platelets in mediating inflammatory cell recruitment in the context of inflammatory and autoimmune diseases.
