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

Abstract

Background: The interaction between leucocytes and vascular endothelial cells is essential for leucocyte migration into inflammatory sites.

Aims: 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.

Figures

Figure 1

Density of CD3+ T cells in the lamina propria of the colon (A) and jejunum (B) of controls and patients with inflammatory bowel disease.

Figure 2

Density of intercellular adhesion molecule (ICAM) 1+ vessels in the lamina propria of the colon (A) and jejunum (B) of controls and patients with inflammatory bowel disease.

Figure 3

Density of α4β7+ cells in the lamina propria of the colon (A) and jejunum (B); and of mucosal addressin cell adhesion molecule (MAdCAM)-1+ vessels in the lamina propria of the colon (C) and jejunum (D) in controls and patients with inflammatory bowel disease.

Figure 4

OX40L+ vessels in the colonic mucosa of patients with inflammatory bowel disease. (A) An OX40L+ vessel in the lamina propria of the colon of a patient with ulcerative colitis. (B) Section from a patient with ulcerative colitis which was stained with human control IgG; the vessel is arrowed. (C) Section from the colon of a patient with irritable bowel syndrome stained for OX40L expression. The unstained vessel is also arrowed. The non-specific staining is due to antibody binding to epithelial mucus; this is not seen in A and B because of the mucus depletion associated with ulcerative colitis. Original magnification × 400.

Figure 5

Density of OX40+ cells in the lamina propria of the colon (A) and jejunum (B); and of OX40L+ vessels in the colon (C) in controls and patients with inflammatory bowel disease.

Figure 6

Density of OX40+ cells in the lamina propria and submucosa of patients with Crohn's disease.