Activated leucocytes express and secrete macrophage inflammatory protein-1 upon interaction with synovial fibroblasts of rheumatoid arthritis via a 2-integrin/ICAM-1 mechanism

Abstract

Objective. To examine the expression and regulation of chemotactic factor, macrophage inflammatory protein-1α (MIP-1α) by fibroblast-like synoviocytes (FLS), monocytes and polymorphonuclear neutrophils (PMN) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Methods. Monocytes or PMN obtained from RA SF were co-cultured with unstimulated semiconfluent RA FLS. Culture supernatants were assayed for MIP-1α by enzyme-linked immunosorbent assay. The expression of MIP-1α mRNA and protein was also determined by Northern blot analyss and immunohistochemistry respectively. Results. Interaction of activated leucocytes with FLS synergistically increased MIP-1α expression and secretion via a mechanism mediated by β₂-integrin/ intercellular adhesion molecule 1. Conclusion. MIP-1α expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leucocytes and FLS, and plays a crucial role in the progression and maintenance of RA synovitis.