IL-1-BETA-CONVERTING ENZYME (ICE) IS PRESENT AND FUNCTIONAL IN HUMAN ALVEOLAR MACROPHAGES - MACROPHAGE IL-1-BETA RELEASE LIMITATION IS ICE INDEPENDENT

Tissue macrophages readily produce intracellular pro-IL-1 beta in resp onse to stimuli such as LPS, but are limited in mature IL-1 beta relea se compared with blood monocytes. The mechanism of this IL-1 beta cont rol may provide important insights into the physiology of IL-1 beta at the tissue level. Since it has been hypothesized that IL-1 beta proce ssing by the IL-lp-converting enzyme (ICE) regulates IL-1 beta release , we compared human alveolar macrophages and human blood monocytes for relative ICE expression and activation. Using immunoblots and enzyme- linked immunoassay for ICE, we demonstrate that alveolar macrophages d o not differ from blood monocytes in antigenic p45 ICE. Furthermore, a n indirect assay for functional ICE documents similar ICE activities i n both monocytes and alveolar macrophages, i.e., similar concentration s of soluble synthetic ICE inhibitor (IC,, values of 0.3 +/- 0.01 and 0.6 +/- 0.2 mu M, respectively) are required to block mature IL-1 beta generation. However, as has been reported for THP-1 myelomonocytic ce lls, neither alveolar macrophages nor blood monocytes contain directly quantifiable levels of functional ICE forms (p22/p20 and p10) when as sayed by immunoblots or by a sensitive capture ELISA that uses an irre versible, biotinylated ICE inhibitor. These findings document that the macrophage limitation in mature IL-1 beta release is not due to a lac k of ICE or to an inability to activate ICE, Finally, using a staged r elease assay, the time to half-maximum mature IL-1 beta release is sig nificantly depressed in macrophages compared with that in monocytes. T aken together, these findings suggest that macrophage IL-1 beta export is regulated independently of ICE activation.