The human peripheral lymph node vascular addressin an inducible endothelial antigen involved in lymphocyte homing

Sara A. Michie, Philip Streeter, Patricia A. Bolt, Eugene C. Butcher, Louis Picker

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

The extravasation of blood-borne lymphocytes into organized lymphoid tissues and sites of chronic inflammation is directed in part by interactions of lymphocyte surface adhesion molecules, known as homing receptors, with tissue-selective endothelial ligands called vascular addressing. In mice and humans, lymphocyte L-selectin and the peripheral lymph node addressin (PNAd) form a homing receptor-endothelial ligand pair involved in lymphocyte traffic to peripheral lymph node (PLN). We have examined the tissue distribution and function of human PNAd, using monoclonal antibody MECA-79 and in vitro assays of L-selectin-dependent lymphocyte binding. We demonstrate that PNAd is expressed by human high endothelial venules (HEV) in lymphoid tissues which support lymphocyte adhesion via a PLN-associated recognition system. MECA-79 inhibits adhesion to these HEV of a cell line that binds predominantly via the PLN-homing receptor, L-selectin, but has no effect on adhesion by a mucosal HEV-binding cell line. Furthermore, MECA-79 blocks binding of human peripheral blood mononuclear cells to both PLN and tonsil HEV, but not significantly to HEV in the appendix. In addition, we demonstrate PNAd induction on venules at chronic inflammatory sites in humans, particularly sites with se- vere or long-standing chronic inflammatory involvement. These results confirm that PNAd functions as a PLN vascular addressin in humans, and that in addition to directing normal lymphocyte recirculation to lymph nodes and tonsils, this addressin likely participates in lymphocyte recruitment to sites of chronic inflammation.

Original languageEnglish (US)
Pages (from-to)1688-1698
Number of pages11
JournalAmerican Journal of Pathology
Volume143
Issue number6
StatePublished - 1993
Externally publishedYes

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Lymphocytes
Venules
Antigens
L-Selectin
Lymph Nodes
Palatine Tonsil
Lymphoid Tissue
Lymphocyte Homing Receptors
L-selectin counter-receptors
Ligands
Inflammation
Cell Line
Appendix
Tissue Distribution
Blood Vessels
Blood Cells
Monoclonal Antibodies

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

The human peripheral lymph node vascular addressin an inducible endothelial antigen involved in lymphocyte homing. / Michie, Sara A.; Streeter, Philip; Bolt, Patricia A.; Butcher, Eugene C.; Picker, Louis.

In: American Journal of Pathology, Vol. 143, No. 6, 1993, p. 1688-1698.

Research output: Contribution to journalArticle

Michie, Sara A. ; Streeter, Philip ; Bolt, Patricia A. ; Butcher, Eugene C. ; Picker, Louis. / The human peripheral lymph node vascular addressin an inducible endothelial antigen involved in lymphocyte homing. In: American Journal of Pathology. 1993 ; Vol. 143, No. 6. pp. 1688-1698.
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