GlyCAM-1 supports leukocyte rolling in flow: evidence for a greater dynamic stability of L-selectin rolling of lymphocytes than of neutrophils.
L-selectin plays a major role in leukocyte traffic through lymph node high endothelial venules (HEV). We have investigated the role of GlyCAM-1, a major L-selectin ligand produced by HEV, in mediating leukocyte rolling under in vitro flow conditions. Purified GlyCAM-1 was found to support tethering and rolling in physiological shear flow of both human and murine L-selectin expressing leukocytes at an efficiency comparable to the HEV-derived L-selectin ligands termed peripheral node addressin (PNAd). Major dynamic differences between L-selectin rolling of peripheral blood T lymphocytes and neutrophils expressing similar L-selectin level were observed on GlyCAM-1. Lymphocytes established slower and more shear resistant rolling than neutrophils and could roll on GlyCAM-1 at shear stresses lower than the threshold values required for L-selectin-mediated neutrophil rolling. Notably, high stability of L-selectin rolling of lymphocytes requires intact cellular energy, although initial lymphocyte tethering to L-selectin ligands is energy-independent. By contrast, L-selectin mediated rolling of neutrophils is insensitive to energy depletion. The distinct dynamic behavior and energy-dependence of L-selectin rolling in different leukocytes suggest that L-selectin adhesiveness in shear flow is regulated in a cell-type specific manner. The greater stability of L-selectin rolling of lymphocytes on surface-adsorbed GlyCAM-1 may contribute to their selective recruitment at peripheral lymph nodes.
Dwir
O
O
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Shimron
F
F
Chen
C
C
Singer
M S
MS
Rosen
S D
SD
Alon
R
R
D000818:Animals; D000954:Antigens, Surface / Q000494:pharmacology; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D018056:Hemorheology; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D009077:Mucins; D019041:L-Selectin; C075185:sulfated glycoprotein p50