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Expression of the alphaEbeta7 integrin by mast cells in rheumatoid synovium
K A Gibson1, R K Kumar, N Tedla
1Inflammation Research Unit, The University of New South Wales, Sydney, Australia.
Objective:
Rheumatoid synovitis is characterized by a mast cell response in which tryptase containing mast cells (MCT) associate with T lymphocyte infiltration, and tryptase and chymase containing mast cells (MCTC) correlate more closely with tissue damage or repair events. We investigated expression of the alphaEbeta7 integrin and its ligand E-cadherin in rheumatoid and normal synovium and compared this expression to synovial mast cell responses.
Methods:
Immunohistochemical analysis was used to determine the expression of alphaEbeta7 and E-cadherin in rheumatoid (n = 17) and normal (n = 6) synovium. The density of MCT and MCTC mast cell subsets was compared to the density of alphaEbeta7 positive mast cells.
Results:
The mean density of alphaEbeta7 positive cells in rheumatoid synovia was 25.2 cells/mm2 (range 0.3-102.9), of which 26.7% (range 0-68.6%) were mast cells. A mean of 11.9% (range 0-30.4%) of rheumatoid synovial mast cells expressed alphaEbeta7 compared to 0% in normal synovium (p < 0.0001). There was a strong correlation between the density of alphaEbeta7 positive cells and the total mast cell density in rheumatoid synovium (r2= 0.74). alphaEbeta7 positive mast cell density correlated significantly with the MCT subset density (r2 = 0.5, p = 0.014), but not with the MCTC subset density. E-cadherin expression was increased in rheumatoid compared with normal synovium, but did not colocalize or correlate with alphaEbeta7 expression.
Conclusion:
These results indicate a role for alphaEbeta7 in the mast cell response that occurs in rheumatoid synovitis, in particular the MCT mast cell subset expansion associated with inflammatory events and interactions with infiltrating lymphocytes.