Identification of a high-affinity receptor for interleukin 1α and interleukin 1β on cultured human rheumatoid synovial cells

Abstract

In this report the binding of recombinant human interleukins 1α and 1β (rIL-1α and rIL-1β) to primary cultures of human rheumatoid synovial cells is measured and compared to the concentrations of these mediators required for stimulation of PGE2 production by these same cells. The average concentration of IL-1α required for half-maximal stimulation of PGE2 was 4.6 ± 1.5 pM (± SEM) (n = 6), whereas for IL-1β half-maximal stimulation was observed at a concentration of 1.3 ± 0.24 pM (n = 6). Both direct and competitive binding experiments were performed. In direct binding experiments, IL-1α bound with a K(d) of 66 pM (n = 1), while IL-1β bound with a K(d) of 4 pM (n = 2). In competitive binding experiments, IL-1α inhibited binding of 125I-I-IL-1α with a K(i) of 33-36 pM (n = 2) and binding of a125I-IL-1β with a K(i) of 51-63 pM (n = 2). Il-1β inhibited binding of 125I-IL-1α with a K(i) of 2-3 pM (n = 2) and binding of 125I-IL-1β with a K(i) of 7 pM (n = 2). The binding data were best fit by a model specifying a single class of receptors with homogeneous affinity for either IL-1α or IL-1β and with an abundance of 3,000-14,000 sites per cell. Autoradiography showed that the vast majority of the synoviocytes within the cultures possessed IL-1 receptors. Comparison of biological response curves with the binding curves indicates that the observed receptors exhibit sufficiently high affinity to mediate the response of human synoviocytes to low picomolar concentrations of IL-1α and IL-1β.