Expression of GlyCAM-1, an endothelial ligand for L-selectin, is affected by afferent lymphatic flow.
The interaction of naive, L-selectin-bearing lymphocytes with counterreceptors on the surface of high endothelial venules (HEV) is the initial step in the extravasation of these cells from the bloodstream into the peripheral lymph node. Recently, two sulfated glycoprotein ligands, 50 and 90 kDa, respectively, have been identified as ligands for L-selectin using an L-selectin-IgG chimera. cDNA cloning of one of these molecules, the 50-kDa sulfated glycoprotein (glycosylation-dependent cell adhesion molecule 1 [GlyCAM-1]), has shown it to be a mucinlike scaffold that presents a carbohydrate ligand(s) to the lectin domain of L-selectin. Herein, we analyze the factors that might regulate the expression of these ligands. Ligation of afferent lymphatics results in a complete loss of the mRNA for GlyCAM-1. In addition, L-selectin-mediated adhesion, as inferred by binding of an L-selectin-IgG chimera, is also lost on interruption of afferent flow. It thus appears that a soluble and/or cellular component(s) of afferent lymph regulates the expression of GlyCAM-1 mRNA and the resultant HEV adhesiveness for lymphocytes.
Mebius
R E
RE
Department of Pathology and Developmental Biology, Stanford University, CA 94305.
Dowbenko
D
D
Williams
A
A
Fennie
C
C
Lasky
L A
LA
Watson
S R
SR
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019041:L-Selectin; D008024:Ligands; D008196:Lymph / Q000502:physiology*; D008208:Lymphatic System / Q000502:physiology; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; D008024:Ligands; D009077:Mucins; D012333:RNA, Messenger; D019041:L-Selectin; C075185:sulfated glycoprotein p50