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Am J Gastroenterol. 2007 Jul;102(7):1499-509. Epub 2007 Apr 24.

Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis.

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1
Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.

Abstract

OBJECTIVES:

In the colonic mucosa with ulcerative colitis (UC), it has been suggested that L-selectin-peripheral lymph node addressin (PNAd) interaction plays a role in lymphocyte recruitment, which requires PNAd induction on high endothelial venule (HEV)-like vessels. The present study was undertaken to elucidate how these HEV-like vessels participate in the pathogenesis of UC and also to determine whether the presence of such vessels is correlated with clinical outcomes.

METHODS:

Biopsy specimens composed of active (N = 32) and remission (N = 12) phases of UC were subjected to immunohistochemistry for CD34, MECA-79, and HECA-452, and the immunostained sections were quantitatively analyzed. An in vitro binding assay with L-selectin*IgM chimeric protein was carried out to determine whether PNAd on HEV-like vessels formed in UC functions as an L-selectin ligand. RT-PCR was carried out to determine which enzyme is upregulated for PNAd biosynthesis on HEV-like vessels induced in the active phase of UC. Triple immunostaining for MECA-79 together with CD3 and CD20/CD79alpha, CD4 and CD8, or CXCR3 and ST2L was carried out to determine which lymphocyte population closely associates with these vessels.

RESULTS:

PNAd-expressing HEV-like vessels were preferentially induced in the active phase of UC with increased transcription of the gene encoding N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1, which directs expression of the MECA-79 epitope. Moreover, T cells, particularly CD4(+) T cells, were more closely associated with these HEV-like vessels than B cells.

CONCLUSIONS:

T-cell recruitment via PNAd-expressing HEV-like vessels induced by expression of GlcNAc6ST-1 may play a role in UC pathogenesis.

[Indexed for MEDLINE]

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