OBJECTIVES: The pattern of angiotensin-converting enzyme (ACE) expression in dendritic cells (DC) and macrophages derived from normal monocytes vs that in DC derived from acute myeloid leukemia blasts was investigated. MATERIALS AND METHODS: ACE expression was quantified by flow cytometry using a set of monoclonal antibodies (mAbs) directed against five different epitopes on the ACE molecule and by enzyme activity measurement. RESULTS: The binding pattern of a set of anti-ACE mAbs to the surface of blood cells and their progeny, as revealed by FACS, showed lineage and epitope specificity. Differentiation of monocytes to macrophages and DC was accompanied by a dramatic increase in ACE expression. ACE activity was 50-fold higher in macrophages and 150-fold higher in DC than in monocytes. ACE level normalized per cell revealed that DC expressed 1300-fold more ACE than did monocytes. In contrast, DC derived from acute myeloid leukemia blasts did not show an elevated level of ACE, although they acquired DC markers CD80, CD40, and CD86 upon cytokine or calcium ionophore treatment. CONCLUSIONS: ACE expression becomes the first marker to functionally distinguish DC generated from monocytes and leukemic blast cells. Given that ACE plays an important role in the hydrolysis of many peptides, as well as in the presentation of some antigens to immune cells, these data suggest that elevated ACE expression on the surface of DC is not just a reflection of the general activation of monocytes during differentiation; rather, it may be physiologically important for the functioning of these cells.
OBJECTIVES: The pattern of angiotensin-converting enzyme (ACE) expression in dendritic cells (DC) and macrophages derived from normal monocytes vs that in DC derived from acute myeloid leukemia blasts was investigated. MATERIALS AND METHODS:ACE expression was quantified by flow cytometry using a set of monoclonal antibodies (mAbs) directed against five different epitopes on the ACE molecule and by enzyme activity measurement. RESULTS: The binding pattern of a set of anti-ACE mAbs to the surface of blood cells and their progeny, as revealed by FACS, showed lineage and epitope specificity. Differentiation of monocytes to macrophages and DC was accompanied by a dramatic increase in ACE expression. ACE activity was 50-fold higher in macrophages and 150-fold higher in DC than in monocytes. ACE level normalized per cell revealed that DC expressed 1300-fold more ACE than did monocytes. In contrast, DC derived from acute myeloid leukemia blasts did not show an elevated level of ACE, although they acquired DC markers CD80, CD40, and CD86 upon cytokine or calcium ionophore treatment. CONCLUSIONS:ACE expression becomes the first marker to functionally distinguish DC generated from monocytes and leukemic blast cells. Given that ACE plays an important role in the hydrolysis of many peptides, as well as in the presentation of some antigens to immune cells, these data suggest that elevated ACE expression on the surface of DC is not just a reflection of the general activation of monocytes during differentiation; rather, it may be physiologically important for the functioning of these cells.
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Authors: Andrew B Nesterovitch; Kyle D Hogarth; Vyacheslav A Adarichev; Elena I Vinokour; David E Schwartz; Julian Solway; Sergei M Danilov Journal: PLoS One Date: 2009-12-14 Impact factor: 3.240