gms | German Medical Science

Dendritic cells (DCs) are the most potent antigen-presenting cells of the mammalian immune system. Recently, it has been demonstrated that DCs not only link components of innate with adaptive immunity, but might play a role in the cardiovascular system suggesting a link with pathogenic principles of atherosclerosis. Here we studied the expression of ACE on these specialized cells. Myeloid DCs were obtained by incubation of human peripheral blood monocytes with GM-CSF and IL-4. After 5-7 days immature DCs were obtained exhibiting high macropinocytotic activity and expression of CD1a. While resting monocytes did not express ACE on their surface at all, immature DC expressed extremely high amounts of ACE, which was even in excess to control endothelial cells. Increased expression was verified on the transcriptional level by real time PCR. Interestingly, after DC maturation with LPS or CD40-ligation ACE surface molecule expression was markedly down-regulated. Since Vitamin-D3 has been previously demonstrated to block DC differentiation and DC maturation, we added this compound to DCs during the differentiation and maturation phase. We observed a complete inhibition of ACE expression in DCs and interestingly an impaired suppression of ACE downregulation upon maturation stimuli. Since angiotensin-II is a well-described major proinflammatoty peptide, it is suggested that in vitamin-D3-deficient states the number of "proinflammatory" DCs in the periphery might be increased such as in patients with chronic renal insufficiency.