A novel endothelial L-selectin ligand activity in lymph node medulla that is regulated by alpha(1,3)-fucosyltransferase-IV.
Lymphocytes home to peripheral lymph nodes (PLNs) via high endothelial venules (HEVs) in the subcortex and incrementally larger collecting venules in the medulla. HEVs express ligands for L-selectin, which mediates lymphocyte rolling. L-selectin counterreceptors in HEVs are recognized by mAb MECA-79, a surrogate marker for molecularly heterogeneous glycans termed peripheral node addressin. By contrast, we find that medullary venules express L-selectin ligands not recognized by MECA-79. Both L-selectin ligands must be fucosylated by alpha(1,3)-fucosyltransferase (FucT)-IV or FucT-VII as rolling is absent in FucT-IV+VII(-/-) mice. Intravital microscopy experiments revealed that MECA-79-reactive ligands depend primarily on FucT-VII, whereas MECA-79-independent medullary L-selectin ligands are regulated by FucT-IV. Expression levels of both enzymes paralleled these anatomical distinctions. The relative mRNA level of FucT-IV was higher in medullary venules than in HEVs, whereas FucT-VII was most prominent in HEVs and weak in medullary venules. Thus, two distinct L-selectin ligands are segmentally confined to contiguous microvascular domains in PLNs. Although MECA-79-reactive species predominate in HEVs, medullary venules express another ligand that is spatially, antigenically, and biosynthetically unique. Physiologic relevance for this novel activity in medullary microvessels is suggested by the finding that L-selectin-dependent T cell homing to PLNs was partly insensitive to MECA-79 inhibition.
CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.
Christine
C
M'Rini
Guiying
G
Cheng
Colleen
C
Schweitzer
Lois L
LL
Cavanagh
Roger T
RT
Palframan
Thorsten R
TR
Mempel
Richard A
RA
Warnock
John B
JB
Lowe
Elizabeth J
EJ
Quackenbush
Ulrich H
UH
von Andrian
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000378:metabolism*; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008198:Lymph Nodes / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000954:Antigens, Surface; D017931:DNA Primers; C069886:L-selectin counter-receptors; D008024:Ligands; D008565:Membrane Proteins; D019041:L-Selectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase