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

• Published in: The Journal of experimental medicine Vol. 177; no. 3; pp. 833 - 838
• Main Authors: KANSAS, G. S, LEY, K, MUNRO, J. M, TEDDER, T. F
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.03.1993; The Rockefeller University Press
• Subjects: Actin Cytoskeleton - drug effects; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - pharmacology; Cell Line; Cell Movement - drug effects; Cell Movement - physiology; Cytochalasin B - pharmacology; Cytoplasm - chemistry; DNA - genetics; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Endothelium, Vascular - ultrastructure; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunohematology; Inflammation - pathology; L-Selectin; Leukocyte immunology; Leukocytes - cytology; Leukocytes - physiology; Leukocytes - ultrastructure; Lymphatic System; Mice; Molecular Sequence Data; Precipitin Tests; Human; Lymph node; Leukocyte; Rodentia; Biological marker; Cell cell interaction; Inflammation; Venule; Adhesion; Endothelium; Vertebrata; Mammalia; Structure activity relation; Mouse; Aminoacid sequence
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.177.3.833

L-selectin (leukocyte adhesion molecule 1/MEL-14), a member of the selectin 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-selectin between humans and mice suggests an important role for this region. Deletion of the COOH-terminal 11 amino acids from the approximately 17 amino acid cytoplasmic domain of L-selectin eliminated 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 L-selectin. Pretreatment of cells with cytochalasin B, which disrupts actin microfilaments, also abolished adhesion without affecting carbohydrate recognition. Therefore, the cytoplasmic domain of L-selectin regulates leukocyte adhesion to endothelium independent of ligand recognition, by controlling cytoskeletal interactions and/or receptor avidity.