ANGIOTENSIN-CONVERTING ENZYME (KININASE-II) MESSENGER-RNA PRODUCTION AND ENZYMATIC-ACTIVITY IN HUMAN PERIPHERAL-BLOOD MONOCYTES ARE INDUCEDBY GM-CSF BUT NOT BY OTHER CYTOKINES

Peripheral blood monocytes (PBM) do not possess angiotensin converting enzyme (ACE) activity in the inactive state. However, measurable PBM ACE activity is found in patients with certain inflammatory diseases. We have examined the effect of cytokines likely to be present during g ranulomatous inflammation on the regulation of ACE mRNA in PBM. The pr esence of ACE mRNA in human PBM cultured in vitro with various cytokin es for up to 6 days was analyzed using polymerase chain reaction. PBM not exposed to cytokines did not express ACE mRNA, while incubation of PBM with recombinant human GM-CSF resulted in high levels of ACE mRNA expression after 72 h of cell culture, which persisted through day si x. Increased ACE mRNA expression occurred concommitantly with phenotyp ic changes in cell size and shape consistent with cell activation. A 5 -fold increase in ACE enzymatic activity also occurred. Incubation of PBM with all other cytokines tested failed to induce ACE mRNA expressi on. Alveolar macrophages expressed ACE mRNA immediately following thei r isolation, but mRNA expression decreased markedly during a 24-h peri od of incubation and was only partially reversed with exogenous GM-CSF . We conclude that GM-CSF enhances ACE mRNA levels in human PBM, but n ot in alveolar macrophages.