Artikel
Renin induces ERK 1/2 phosphorylation in U937 monocyte/macrophages independent of angiotensin II
Reninstimulation führt unabhänging von Angiotensin II zur ERK1/2-Phosphorylierung in U937 Makrophagen
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Veröffentlicht: | 11. November 2004 |
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Gliederung
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The "renin receptor" (RER) was recently cloned. RER mediates effects by activating MAP kinases and facilitates cell-surface angiotensin (Ang) II generation. We studied RER in freshly isolated human blood cells and several cell lines. We used TaqMan RT-PRC, FACS analysis for RER detection and analyzed ERK 1/2 phosphorylation after stimulation with human recombinant renin. RER mRNA was expressed in human T-cells, macrophages, granulocytes, and U937 monocyte Jurkat cell lines. RER, analyzed by FACS, is expressed on macrophages, T-cells, and granulocytes. However, fluorescence was detected only after the cells were permeablized before staining. We next investigated U937 macrophages in more detail. We differentiated U937 monocytes into macrophages by PMA stimulation to see if the RER translocates to the the cell surface. However, this was not the case. We next investigated ERK 1/2 phosphorylation in U937 monocytes and macrophages. Renin (10 nM), in the presence of an ACE inhibitor and AT1 receptor blocker, increased ERK 1/2 phosphorylation, while unphosphorylated ERK was not affected. We also investigated cell signaling with deglycosylated renin to test the hypothesis whether the manose-6-phosphate receptor mediates cellular renin uptake. However, deglycosylated renin induced ERK 1/2 phosphorylation in a similar fashion as glycosylated renin. We show that circulating blood cells express the RER. Glycosylated and deglycosylated renin (10 nM) induces ERK 1/2 phosphorylation in U937 monocytes and macrophages independent of Ang II, indicating that the manose-6-phosphate receptor is not involved.