Upregulation of renin-angiotensin system during differentiation of monocytes to macrophages.

作者: Atsunori Okamura , Hiromi Rakugi , Mitsuru Ohishi , Yoshihiro Yanagitani , Shin Takiuchi

DOI: 10.1097/00004872-199917040-00012

关键词: MonocyteAngiotensin II receptor type 1Renin–angiotensin systemAngiotensin IIMacrophageAngiotensin-converting enzymeBiologyInternal medicineChymaseEndocrinologyU937 cell

摘要: Background We have demonstrated that accumulated macrophages in human coronary arteries strongly express angiotensin converting enzyme accordance with the development of atheromatous plaques. However, there are few reports on regulation renin-angiotensin system and monocytes as their source. Objective To examine whether is upregulated during differentiation to macrophages, it further regulated by II cytokines. Materials methods used a leukemia cell line, THP-1, for monocytes. Differentiated induced adding phorbol 12-myristate 13-acetate 24 h, were macrophages. Expression messenger RNA components was measured quantitative reverse-transcriptase polymerase chain reaction. Angiotensin activity subtype-specific angiotensin-binding sites cultured cells, production culture medium measured. Results Macrophages expressed all except chymase. Cellular increased 3.2- 4.5-fold differentiation, respectively. type 1 (AT1) 2 (AT2) receptors 6.2-and 6.4-fold sustained 7 days. Incubation h caused downregulation both AT1 AT2 receptor RNA, but expression levels still more than threefold higher compared The density binding 0.26 +/- 0.02 0.15 0.01 fmol/10(6) Conclusion markedly activated monocyte/macrophage may participate atherosclerosis.

参考文章(43)
O Costerousse, J Allegrini, M Lopez, F Alhenc-Gelas, Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochemical Journal. ,vol. 290, pp. 33- 40 ,(1993) , 10.1042/BJ2900033
B Bouscarel, P B Wilson, P F Blackmore, C J Lynch, J H Exton, Agonist-induced down-regulation of the angiotensin II receptor in primary cultures of rat hepatocytes. Journal of Biological Chemistry. ,vol. 263, pp. 14920- 14924 ,(1988) , 10.1016/S0021-9258(18)68126-8
J. A. Madri, L. Bell, Influence of the angiotensin system on endothelial and smooth muscle cell migration. American Journal of Pathology. ,vol. 137, pp. 7- 12 ,(1990)
Franklin H. Epstein, Daniel Steinberg, Sampath Parthasarathy, Thomas E. Carew, John C. Khoo, Joseph L. Witztum, Beyond Cholesterol New England Journal of Medicine. ,vol. 320, pp. 915- 924 ,(1989) , 10.1056/NEJM198904063201407
H Rakugi, H J Jacob, J E Krieger, J R Ingelfinger, R E Pratt, Vascular injury induces angiotensinogen gene expression in the media and neointima. Circulation. ,vol. 87, pp. 283- 290 ,(1993) , 10.1161/01.CIR.87.1.283
K Sassaki, Y Yamono, S Bardhan, N Iwai, JJ Murray, M Hasegawa, Y Matsuda, T Inagami, None, Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor Nature. ,vol. 351, pp. 230- 233 ,(1991) , 10.1038/351230A0
R Morishita, G H Gibbons, K E Ellison, W Lee, L Zhang, H Yu, Y Kaneda, T Ogihara, V J Dzau, Evidence for direct local effect of angiotensin in vascular hypertrophy. In vivo gene transfer of angiotensin converting enzyme. Journal of Clinical Investigation. ,vol. 94, pp. 978- 984 ,(1994) , 10.1172/JCI117464
S. Yusuf, C.J. Pepine, C. Garces, H. Pouleur, M. Rousseau, D. Salem, J. Kostis, C. Benedict, M. Bourassa, B. Pitt, Effect of Enalapril On Myocardial-infarction and Unstable Angina in Patients With Low Ejection Fractions The Lancet. ,vol. 340, pp. 1173- 1178 ,(1992) , 10.1016/0140-6736(92)92889-N