title: Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis.
abstract: OBJECTIVE
  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.
authors: Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Kenichi
authors: K
authors: Suzawa
authors: Motohiro
authors: M
authors: Kobayashi
authors: Yasuhiro
authors: Y
authors: Sakai
authors: Hitomi
authors: H
authors: Hoshino
authors: Matsuko
authors: M
authors: Watanabe
authors: Oi
authors: O
authors: Harada
authors: Haruo
authors: H
authors: Ohtani
authors: Minoru
authors: M
authors: Fukuda
authors: Jun
authors: J
authors: Nakayama
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin; D017705:Lignans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012313:RNA / Q000235:genetics; D016201:Receptors, Lymphocyte Homing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015238:Sulfotransferases / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D014699:Venules / Q000378:metabolism* / Q000473:pathology; D000097811:Carbohydrate Sulfotransferases
chemical_list: D018952:Antigens, CD34; D000954:Antigens, Surface; D019041:L-Selectin; D017705:Lignans; D008565:Membrane Proteins; D012313:RNA; D016201:Receptors, Lymphocyte Homing; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C069886:L-selectin counter-receptors