Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis

Abstract

Aim: The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin alpha4beta7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT). Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center, strongly associated with H pylori infection. The purpose of this study was to address the implication of the MAdCAM-1/integrin beta7 pathway in NG.

Methods: We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls. A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM-1 and integrin beta7. In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated. We also performed immunostaining with anti-CD20, CD4, CD8 and CD68 antibodies to determine the lymphocyte subsets co-expressing integrin beta7.

Results: Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection. Of note, the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls. Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates. Integrin beta7-expressing mononuclear cells, mainly composed of CD20 and CD4 lymphocytes, were associated with vessels lined with MAdCAM-1-expressing endothelium.

Conclusion: Our results suggest that the MAdCAM-1/integrin alpha4beta7 homing system may participate in gastric inflammation in response to H pylori-infection and contributes to MALT formation, typically leading to the development of NG.

Figure 1

(A): H pylori-negative gastric mucosa showed little immunoreactivity for mucosal addressin cell adhesion mol-ecule 1 (MAdCAM-1). MAdCAM-1 was expressed on the en-dothelium of numerous vessels within the lamina propria with H pylori infection (B), particularly in association with dense mononuclear infiltration (C). Strong endothelial expres-sion of MAdCAM-1 was localized on high endothelial venule-like vessels adjacent to the lymphoid follicles D.

Figure 2

MAdCAM-1 immunoreactivity on mucosal vascula-ture of antral biopsy specimens from patients with nodular gas-tritis and H pylori-positive and –negative controls. Results were expressed as the percentage of von-Willebrand factor-positive vessels immunoreactive for MAdCAM -1 in serial sections.

Figure 3

In simultaneous viewing of serial sections, integrin β7-expressing cells (A) consisted of CD-4-positive T lymphocytes (B).

Figure 4

Vessels lined with MAdCAM-1-positive endothelium (A) were associated with infiltration of lymphocytes immu-noreactive for integrin β7 (B).

Figure 5

MAdCAM-1 and glyceraldehyde-3-phosphate dehy-drogenase (G3PDH) mRNA transcripts were detected as 387 and 983 base pair-bands with reverse transcriptase-polymerase chain reaction, respectively. Lane N: negative control, lane 1: H pylori-negative control, lane 2: H pylori-positive control, lane 3: patients with nodular gastritis.