MODULATION OF LEUKOCYTE TRANSENDOTHELIAL MIGRATION BY INTEGRIN-ASSOCIATED GLYCOSYL PHOSPHATIDYL-INOSITOL (GPI)-ANCHORED PROTEINS

Leukocyte transendothelial migration is an essential process in inflam mation and the immune response. The mechanisms involved in leukocyte a dhesion to the endothelium, forming the first step in leukocyte extrav asation, have been fairly well documented. However, subsequent steps, which include de-adhesion, coupled with locomotion, remain largely unk nown. As part of our efforts to study leukocyte transendothelial migra tion, we previously established a monoclonal antibody (mAb) that seque ntially up-regulates and down-regulates beta(2) integrin-dependent adh esion of human neutrophils, as well as transendothelial migration in v itro. The molecule recognized by this mAb is a glycosyl phosphatidyl i nositol, (GPI)-anchored glycoprotein This protein may prove to be a ne w member of the family of integrin-associated, GPI-anchored proteins, which includes urokinase-type plasminogen activator receptor (uPAR), l ipopolysaccharide (LPS)/LPS binding protein (LBP) receptor (CD14), and Fc gamma receptor IIIB (CD16b); all of which are regulators of integr in function. The mechanisms involved in beta 2 integrin regulation by this new GPI-anchored glycoprotein are discussed.