Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of l-selectin

L-sdectin (leukocyte adhesion molecule 1/MEL14), a member of the sdectin family of cell adhesion molecules, mediates leukocyte rolling and leukocyte adhesion to endothelium at sites of inflammation. In addition, L-selectin mediates the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes. The strong amino acid sequence conservation of the cytoplasmic domain of L-sectin between humans and mice suggests an important role for this region. Deletion of the COOH-terminal 11 amino acids from the ∼17 amino acid cytoplasmic domain of I, sdectin diminated binding of lymphocytes to HEV in the in vitro frozen section assay, and also abolished leukocyte rolling in vivo in exteriorized rat mesenteric venules, but did not alter the lectin activity of bselectin. Pretreatment of ceils with cytochalasin B, which disrupts actin microfilaments, also abolished adhesion without affecting carbohydrate recognition. Therefore, the cytoplasmic domain of I-selectin regulates leukocyte adhesion to endothelium independent ofligand recognition, by controlling cytoskeletal interactions and/or receptor avidity.