REGULATED EXPRESSION AND RELEASE OF THE IL-1 DECOY RECEPTOR IN HUMAN MONONUCLEAR PHAGOCYTES

The aim of this study was to investigate the expression and release of the IL-1 type II decoy receptor (R) in mononuclear phagocytes, which play a central role in immune and chronic inflammatory reactions, Huma n monocytes expressed both type I and type II R transcripts, the latte r being two- to threefold more represented, By cross-linking and Ab bl ocking, the predominant surface IL-1-binding molecule was the decoy RI I. IL-4, IL-13, and dexamethasone induced RI and RII transcripts and a ugmented the number of IL-1-binding sites with no modification of K-d values, The induced surface receptor was identified as the decoy RII. These stimuli induced the release of a soluble R with a m.w. of approx imately 60 kDa, of which N-glycosylation contributed 22 kDa compared w ith 45 kDa released from polymorphonuclear leukocytes, of which N-glyc osylation contributed 15 kDa. IL-13 and dexamethasone induced a releas e of 24 ng/ml/(2) x 10(7) cells (from 8.7 to 43.2 ng/ml) and 25.6 ng/m l/2 x 10(7) cells (from 9.7 to 36.8 ng/ml) of decoy RII in 18 h, respe ctively (six donors), Thus, for instance, IL-13-treated (18 h) cells e xpressed 3.5 x 10(3) sites/cell and released 12 x 10(3) decoy Rll/cell , The released decoy RII from monocytes bound IL-1 alpha and IL-1 rece ptor antagonist 30- and 2-fold less avidly than IL-1 beta, respectivel y, In vitro-matured, monocyte-derived macrophages showed higher levels of surface expression and release of the IL-1 decoy RII, The results show that, on exposure to diverse molecules with anti-inflammatory pro perties, mononuclear phagocytes express and release copious amounts of a novel version of the soluble IL-1 decoy RII.