GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on naive peripheral lymphocytes.
Naive T cells are selectively recruited from the blood into peripheral lymph nodes during lymphocyte recirculation. L-selectin, a lectin-like receptor, mediates the initial attachment of lymphocytes to high endothelial venules (HEV) in lymph nodes. A subsequent step involving the activation of beta 2 integrins has been proposed to facilitate firm adhesion, but the activating signals are poorly understood. We report here that either antibody-mediated cross-linking of L-selectin on human lymphocytes or treatment of the cells with GlyCAM-1, an HEV-derived, secreted ligand for L-selectin, stimulates their binding to ICAM-1 through the beta 2 integrin pathway. Furthermore, GlyCAM-1 causes the rapid expression of a neoepitope on beta 2 integrins associated with a high-avidity state. Naive (CD45RA+), but not memory (CD45R0+) lymphocytes, respond to L-selectin cross-linking or GlyCAM-1 treatment. Thus, the complexing of L-selectin by specific ligands may provide key signals to naive lymphocytes, contributing to their selective recruitment into peripheral lymphoid organs.
Hwang
S T
ST
Department of Anatomy and Program in Immunology, University of California, San Francisco 94143, USA.
Singer
M S
MS
Giblin
P A
PA
Yednock
T A
TA
Bacon
K B
KB
Simon
S I
SI
Rosen
S D
SD
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001360:Avidin / Q000494:pharmacology; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000096:biosynthesis; D006801:Humans; D007152:Immunologic Capping; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism*; D008024:Ligands; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D009077:Mucins / Q000494:pharmacology*; D011485:Protein Binding; D015398:Signal Transduction; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D000939:Epitopes; D008024:Ligands; D009077:Mucins; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D001360:Avidin; C075185:sulfated glycoprotein p50