Role in the insulin regulated aminopeptidase in macrophages.

The renin-angiotensin system (RAS) is involved in the pathogenesis of cardiovascular diseases such as atherosclerosis and hypertension. Until recently, these effects were attributed to the peptide angiotensine II (AngII) via activation of G-protein coupled AT1 receptors. Ang II has an important role in the regulation of cell growth, inflammation (expression of inflammatory mediators). At the moment ou attention is focussed on the 3-8 fragment of Ang II, Ang IV. This peptide has distinct effect and the occurence of high affinity binding sites led to the concept of the AT4 receptor (recently characterized as insulin regulated aminopeptidase, IRAP) Recently it was shown in vascular smooth muscle cells that Ang IV, independently from AT1 receptors, causes the activation of the NF-kB signalling pathway leading to the an enhanced expression of pro-inflammatory factors. Based on preliminary data in which AT4 binding sites were present in a mouse macrophage cell line as well as in 'ex vivo' rodent macrophages, we aim to investigate the functional properties and the physiological role of these binding sites in macrophages. This will enhance our knowledge of the role of the RAS and of IRAP/AT4 in the immune system.