期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 198, 期 9, 页码 1289-1300出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030057
关键词
lymphocyte homing; L-selectin; sulfotransferase; endothelium; MECA79
资金
- NHLBI NIH HHS [R01 HL054936, HL62524, HL54936] Funding Source: Medline
- NIGMS NIH HHS [R01 GM057411, GM57411] Funding Source: Medline
- PHS HHS [R376M23547] Funding Source: Medline
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 lyrnphocyte sticking in HEV, accounting for the diminished lymphocyte homing. Isolated CD34 and GlyCAM-1 from HEC-GlcNAc6ST-/- animals incorporate similar to70% 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 GIcNAc-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.
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