PATHOLOGICAL SIGNIFICANCE OF ELEVATED SOLUBLE CD14 PRODUCTION IN RHEUMATOID-ARTHRITIS - IN THE PRESENCE OF SOLUBLE CD14, LIPOPOLYSACCHARIDES AT LOW CONCENTRATIONS ACTIVATE RA SYNOVIAL FIBROBLASTS

In order to establish what contributes to elevated levels of soluble C D14 (sCD14) in rheumatoid arthritis (RA) plasma, levels of sCD14 were compared in RA-paired plasma and synovial fluids and, further, in the culture supernatants of monocyte-rich fractions from patients with RA and healthy donors, and macrophage-rich fractions from RA synovial tis sues. The results showed elevated sCD14 in RA synovial fluid in 9 of 1 6 paired samples and in RA macrophage-rich fractions, suggesting that elevated sCD14 in RA plasma might be due to the sCD14 production by RA synovial macrophages. From the molecular analysis of elevated sCD14, the proteolytic cleavage of membranous CD 14 (mCD 14) was important in accelerated sCD14 production. Lipopolysaccharides (LPS) at low concen trations and sCD14 increased the ICAM-1 expression on RA synovial fibr oblasts. This result implies that in vivo RA synovial fibroblasts may be sensitive to LPS in the presence of sCD14 and LPS-binding protein ( LBP).