beta 2-microglobulin increases the expression of vascular cell adhesion molecule on human synovial fibroblasts

Background. beta (2)-Microglobulin (beta (2)m) amyloidosis is a destructive articular disease that affects patients on dialysis. The disease presentat ion is similar to ether forms of arthritis in which adhesion molecules are felt to be pathogenic. Therefore, we hypothesized that beta (2)m directly i ncreases the expression of vascular cell adhesion molecule-1 (VCAM-1) by sy novial fibroblasts. We also examined the effect of alteration of beta (2)m by advanced glycation end products on this cellular response. Methods. Human synovial fibroblasts were isolated and incubated with beta ( 2)m with and without alteration with advanced glycation end products. VCAM- 1 expression was determined by immunnhistochemistry, flow cytometry, and We stern blot and Northern blot analyses. Results. beta (2)m increased the protein expression of VCAM-1 by synovial f ibroblasts in a dose-dependent manner, beta (2)m altered with advanced glyc ation end products had no effect. However, all forms of beta (2)m increased VCAM-1 mRNA. beta (2)m also increased the adhesion of peripheral blood mon onuclear cells to synovial fibroblasts. Conclusion. beta (2)m directly increases the expression of VCAM-1 by synovi al fibroblasts, indicating that synovial fibroblasts may play a key role in the pathogenesis of beta (2)m amyloidosis.