title: In situ expression of the cell adhesion molecules in inflammatory bowel disease. Evidence of immunologic activation of vascular endothelial cells.
abstract: BACKGROUND
  The cell adhesion between vascular endothelial cells and leukocytes is an important process for the immuno-inflammatory changes. To clarify the basic features of inflammatory bowel disease (IBD), studies of in situ localization of the cell adhesion molecules are required.
  
  
  METHODS
  We analyzed the immunohistochemical localization of the adhesion molecules (ICAM-1, LFA-1, Mac-1, VCAM-1, VLA-4, P- and E-selectins) in IBD, stressing phenotypical changes of endothelial cells.
  
  
  RESULTS
  In the normal mucosa, ICAM-1 was expressed in capillaries and venules, LFA-1 in some lymphocytes and VLA-4 in most lymphocytes. VCAM-1 was expressed sporadically in venules and constantly in follicular dendritic cells (FDC) in lymphoid follicles. Both E- and P-selectins were sporadically expressed in venules. In actively inflamed mucosa in IBD, a marked increase of all these antigens was observed; ICAM-1+ inflammatory infiltrates (lymphocytes, plasma cells, and macrophages) and ICAM-1+ venules increased paralleled to the degree of inflammation. LFA-1+ and VLA-4+ mononuclear cells and Mac-1+ granulocytes increased in number. However, expression of VCAM-1 in venules or capillaries was not increased. FDC constantly expressed VCAM-1. E- and P-selectins+ venules increased in actively inflamed tissue particularly at the base of ulcers. Immunoelectron microscopy confirmed expression of these antigens along the plasma membranes (functional localization) and in rough endoplasmic reticulum or in perinuclear spaces (localization during the intracellular synthesis).
  
  
  CONCLUSIONS
  Our study suggested that increased expression of the adhesion molecules in IBD promotes the recruitment of granulocytes and lymphocytes through blood vessels and the cell interaction between lymphocytes-antigen presenting cells or among lymphocytes, thereby sustaining the immuno-inflammatory process in IBD. The present study emphasizes the importance of microenvironmental changes including the endothelial activation in the immuno-inflammatory changes.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Ohtani
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Fukushima
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Kitano
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Nagura
mesh_terms: D000328:Adult; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D012016:Reference Values; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1