Immunohistological localization and possible functions of adrenomedullin

In this short review, we describe the distribution of adrenomedullin (AM)-immunoreactive cells in human tissues and their related biological properties, focusing on the blood coagulation and mucosal defense systems. AM is widely distributed in human tissues, especially in cardiovascular and endocrine tissues. Within vessels, AM has been immunohistochemically detected in vascular smooth muscle cells (SMCs) and endothelial cells (ECs). In atherosclerotic lesions, the peptide is present not only in these cells, but also in macrophages, and the most intense AM immunoreactivity is detected in macrophages located in shoulder lesions of atheromatous plaque, which are considered to be rupture-prone regions. AM inhibits tissue factor production, and augments the production and release of tissue factor pathway inhibitor from aortic ECs. AM also induces the release of antithrombin and urokinase-type plasminogen activator from ECs. Taken together, these antithrombotic properties of the peptide are expected to play an important role in the maintenance of blood circulation. Furthermore, AM immunoreactivity is observed in mucosal and glandular epithelia of the gastrointestinal, respiratory and reproductive systems. AM and the proadrenomedullin N-terminal 20 peptide (PAMP) show strong antibacterial activity against Escherichia coli. In addition, AM is also present in the auditory system. These lines of evidence suggest that AM and its related peptides not only play a role in vasodilatation, but also exhibit multiple biological activities in mammals.