Junctional Adhesion Molecule-A Expression in Crohn's Disease and Ulcerative Colitis
A Devanath, C Parkos, J Li, C Cohen, H Liang. Emory University Hospital, Atlanta, GA
Background: Junctional adhesion molecules (JAMs) are transmembrane components of tight junctions that have been implicated in regulating leukocyte migration in tissues. Previous studies have demonstrated that one JAM protein family member JAM-A regulates permeability and inflammation in the intestine of a knockout mouse. Furthermore, a recent study reported downregulation of JAM-A expression within colonic epithelial cells in areas of active intestinal inflammation in a mouse model. Despite these reports, detailed studies of JAM-A expression in human inflammatory bowel disease (IBD) tissues have not been performed.
Design: Fifty resected colons (20 Crohn's disease, 22 ulcerative colitis, 8 non-IBD controls) were examined. Quiescent and active areas were selected from each IBD case. Paraffin-embedded tissues were examined for JAM-A expression using a specific mAb1H2A9 and DAKO Envision+dual link system. This method employs an HRP labeled polymer with prior heat-induced antigen retrieval. Epithelial, endothelial and stromal expression of JAM-A were evaluated semi quantitatively.
Results: We observed upregulation of JAM expression in the subapical tight junction regions of intestinal crypts in regions with active inflammation, particularly in areas adjacent to ulcers. Findings in ulcerative colitis samples were similar to those in Crohn's disease. JAM-A staining was consistently more intense in areas of active inflammation than in quiescent areas. Furthermore, expression of JAM-A in quiescent areas was similar to that in the control group that consisted of normal colonic tissue from non-IBD cases. In addition, we observed increased staining with mAb 1H2A9 in stromal cells within active areas of inflammation and in endothelial cells. A marked increase in staining was also observed focally in the vasculature on the serosal side of intestinal sections of actively diseased IBD samples.
Conclusions: Our findings suggest that JAM-A expression in inflammatory bowel disease is upregulated during the active phase of the disease, which may play an important role in regulation of leukocyte migration and mucosal permeability. Whether these changes in JAM-A expression are directly or indirectly linked to disease pathogenesis requires further study.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 65, Wednesday Morning