Expression of lymphocyte-endothelial receptor-ligand pairs, alpha4beta7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease.
BACKGROUND
The interaction between leucocytes and vascular endothelial cells is essential for leucocyte migration into inflammatory sites.


OBJECTIVE
To study the local expression of the pairs of complementary molecules, alpha4beta7/mucosal addressin cell adhesion molecule (MAdCAM-1) and OX40/OX40 ligand in the lamina propria of the colon and jejunum of patients with inflammatory bowel disease.


METHODS
Ten patients with active ulcerative colitis (UC), nine with active Crohn's disease (CD), and seven irritable bowel syndrome (IBS) controls were submitted to endoscopic and peroral jejunal biopsies. Specimens were immunostained by indirect alkaline phosphatase using antibodies against CD3, intercellular adhesion molecule (ICAM) 1, alpha4beta7, MAdCAM-1, and OX40. An OX40-mouse-IgG fusion protein was used to detect OX40 ligand on frozen sections. Immunohistological analysis was carried out by optical microscopy using a computer assisted image analyser.


RESULTS
Colonic lamina propria of patients with CD and UC showed increased density of CD3+, alpha4beta7+, and OX40+ cells compared with IBS controls. ICAM-1, MAdCAM-1, and OX40 ligand positive vessels were also increased compared with IBS controls. No significant difference was found in the density of any of these cells in the jejunal mucosa of patients compared with IBS controls.


CONCLUSIONS
The expression of MAdCAM-1 and OX40 ligand on gut endothelial and OX40+ cells is increased in sites of mucosal inflammation in patients with inflammatory bowel disease. No evidence was found for increased lamina propria T cells or increased vascular adhesion molecule expression in the proximal intestine of patients with distal inflammatory bowel disease.
Souza
H S
HS
Department of Internal Medicine, University Hospital, Federal University of Rio de Janeiro, Brazil.
Elia
C C
CC
Spencer
J
J
MacDonald
T T
TT
D000328:Adult; D017252:CD3 Complex / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007136:Immunoglobulins / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology; D007583:Jejunum / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009088:Mucoproteins / Q000378:metabolism; D053278:OX40 Ligand; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; D008024:Ligands; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D008562:Membrane Glycoproteins; D009088:Mucoproteins; D053278:OX40 Ligand; D016201:Receptors, Lymphocyte Homing; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C071777:integrin alpha4beta7