Adrenomedullin in monocytes and macrophages: possible involvement of macrophage-derived adrenomedullin in atherogenesis

Macrophages secrete a variety of growth factors, cytokines and vasoactive p eptides, which are related to the progression of atherosclerosis. Adrenomed ullin (ADM) is a potent vasodilator peptide and inhibits proliferation and migration of vascular smooth muscle cells. In this study, we investigated t he production and secretion of ADM by monocytes and macrophages by Northern blot analysis, RIA and immunocytochemistry. Northern blot analysis showed that ADM mRNA was expressed in human monocytes obtained from peripheral blo od and monocyte-derived macrophages. The expression level of ADM mRNA in mo nocyte-derived macrophages was about five times higher than that in monocyt es. Treatment with lipopolysaccharide (100 ng/ml) for 24 h increased ADM mR NA expression levels in both monocytes and monocyte-derived macrophages. Th e levels of immunoreactive ADM in the media of monocyte-derived macrophages were about three times higher than that of monocytes (0.718 +/- 0.046 fmol /24 h/10(5) cells, n = 8 compared with 0.259 +/- 0.018 fmol/24 h/10(5) cell s, n = 8; mean +/- S.E.M., P < 0.01). The secretion was also increased by t reatment with lipopolysaccharide. Immunocytochemistry showed positive ADM i mmunostaining in macrophages in atherosclerotic lesions of human aorta obta ined at autopsy. ADM secreted from activated macrophages may play an inhibi tory role in atherogenesis.