NEUTROPHIL EXPRESSION OF TUMOR-NECROSIS-FACTOR RECEPTORS (TNF-R) AND OF ACTIVATION MARKERS (CD11B, CD43, CD63) IN RHEUMATOID-ARTHRITIS

In vitro analysis of polymorphonuclear neutrophils (PMN) has allowed v arious stages of cell activation to be distinguished, characterized by the expression level of specific membrane markers and of functional r eceptors. Among those, TNF-alpha receptors (TNF-R) are modulated by va rious PMN activators, a mechanism which may be important to control ce ll responses to TNF in inflammatory reactions such as rheumatoid arthr itis (RA). PMN, isolated from the blood of 36 RA patients and from the synovial fluid of 23 of them, were analysed for membrane expression o f the two TNF-R (p55 and p75). Soluble p55 and p75 (sTNF-R) and TNF co ncentrations were measured in the plasma and synovial fluid by specifi c ELISA assays. Our results show that PMN from the blood of RA patient s bear a normal number of TNF-R, with a normal p55/p75 ratio, compared with PMN from normal controls. Soluble TNF-R levels were similar in p atients and normal plasma. In spite of high endogenous TNF concentrati on, patients' circulating PMN were not activated, as shown by a CD11b/ CD18 expression similar to that of control resting cells. In contrast with blood neutrophils, PMN from RA patients' synovial fluids had an a ctivated phenotype, characterized by increased expression of CD11b, de creased expression of leukosialin, CD43, and the appearance on the pla sma membrane of an azurophil granule protein, CD63. High levels of sol uble TNF-R were measured in RA synovial fluids. Nevertheless, membrane TNF-R levels and p55 and p75 proportions were similar to those of PMN from normal blood. These results suggest the existence of regulatory mechanisms which maintain a stable neutrophil expression of TNF-R as w ell as a balance between both types of receptors in inflammatory situa tions where neutrophils are strongly activated.