Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis

Objective. To analyze which physiologic stimuli induce secretion of myeloid -related protein 8 (MRP8) and MRP14, two S100 proteins expressed in neutrop hils and monocytes, and to determine whether serum concentrations of these proteins are reliable parameters for monitoring inflammatory activity in pa uciarticular juvenile rheumatoid arthritis (JRA). Methods. Secretion of MRP8 and MRP14 was analyzed using a coculture system of endothelial cells and monocytes, Concentrations of MRP8/MRP14 in the ser um and synovial fluid of JRA patients or culture medium were determined by enzyme-linked immunosorbent assay. The expression of MRP8 and MRP14 by leuk ocytes in synovial tissue or fluid was investigated using immunohistochemis try. Results. MRP8 and MRP14 were specifically released during interaction of ac tivated monocytes with tumor necrosis factor-stimulated endothelial cells. Secretion was mediated via an increase in intracellular calcium levels in m onocytes, In contrast, contact with resting endothelium inhibited protein k inase C-induced secretion of the proteins by monocytes. In JRA patients, MR P8 and MRP14 were strongly expressed in infiltrating neutrophils and monocy tes within the inflamed joints and could be found in significantly higher c oncentrations in synovial fluid (mean 42,800 ng/ml) compared with serum (2, 060 ng/ml), Concentrations of MRP8/MRP14 in serum correlated well with thos e in synovial fluid (r = 0.78) and, showed a strong correlation with diseas e activity (r = 0.62), After intraarticular triamcinolone therapy, the seru m concentrations of MRP8/MRP14 decreased significantly in therapy responder s, whereas no differences were found in patients who showed no clinical ben efit, Conclusion, MRP8 and MRP14 are specifically released during the interaction of monocytes with inflammatory activated endothelium, probably at sites of local inflammation. Their serum concentrations represent a useful marker f or monitoring local inflammation in JRA.