Lymphocyte-HEV interactions in lymph nodes of a sulfotransferase-deficient mouse.
The interaction of L-selectin expressed on lymphocytes with sulfated sialomucin ligands such as CD34 and GlyCAM-1 on high endothelial venules (HEV) of lymph nodes results in lymphocyte rolling and is essential for lymphocyte recruitment. HEC-GlcNAc6ST-deficient mice lack an HEV-restricted sulfotransferase with selectivity for the C-6 position of N-acetylglucosamine (GlcNAc). HEC-GlcNAc6ST-/- animals exhibit faster lymphocyte rolling and reduced lymphocyte sticking in HEV, accounting for the diminished lymphocyte homing. Isolated CD34 and GlyCAM-1 from HEC-GlcNAc6ST-/- animals incorporate approximately 70% less sulfate than ligands from wild-type animals. Furthermore, these ligands exhibit a comparable reduction of the epitope recognized by MECA79, a function-blocking antibody that reacts with L-selectin ligands in a GlcNAc-6-sulfate-dependent manner. Whereas MECA79 dramatically inhibits lymphocyte rolling and homing to lymph nodes in wild-type mice, it has no effect on HEC-GlcNAc6ST-/- mice. In contrast, in vitro rolling on purified GlyCAM-1 from HEC-GlcNAc6ST-/- mice, although greatly diminished compared with that on the wild-type ligand, is inhibited by MECA79. Our results demonstrate that HEC-GlcNAc6ST contributes predominantly, but not exclusively, to the sulfation of HEV ligands for L-selectin and that alternative, non-MECA79-reactive ligands are present in the absence of HEC-GlcNAc6ST.
Department of Anatomy, Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA.
Annemieke
A
van Zante
Jean-Marc
JM
Gauguet
Annette
A
Bistrup
Durwin
D
Tsay
Ulrich H
UH
von Andrian
Steven D
SD
Rosen
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D008024:Ligands; D008198:Lymph Nodes / Q000098:blood supply* / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019087:Selectins / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014699:Venules / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D019087:Selectins; D015238:Sulfotransferases