TY - JOUR
T1 - Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis
AU - Suzawa, Kenichi
AU - Kobayashi, Motohiro
AU - Sakai, Yasuhiro
AU - Hoshino, Hitomi
AU - Watanabe, Matsuko
AU - Harada, Oi
AU - Ohtani, Haruo
AU - Fukuda, Minoru
AU - Nakayama, Jun
PY - 2007/7
Y1 - 2007/7
N2 - 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-selectiṅIgM 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/CD79α, 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.
AB - 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-selectiṅIgM 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/CD79α, 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.
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U2 - 10.1111/j.1572-0241.2007.01189.x
DO - 10.1111/j.1572-0241.2007.01189.x
M3 - Article
C2 - 17459027
AN - SCOPUS:34250890337
VL - 102
SP - 1499
EP - 1509
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
SN - 0002-9270
IS - 7
ER -