Monocyte- and cytokine-induced downregulation of angiotensin-converting enzyme in cultured human and porcine endothelial cells

Andreas Papapetropoulos, Alexander Antonov, Renu Virmani, Frank D. Kolodgie, David H. Munn, Nandor Marczin, James W. Ryan, Ross G. Gerrity, John D. Catravas

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We investigated the effects of monocytes on endothelial cell (EC) ectoenzyme activity. Coculture of human aortic ECs with human monocytes (2 x 105 monocytes per 2-cm2 well) led to a decrease in EC angiotensin- converting enzyme (ACE) activity (64.5±3.5% of control) but not aminopeptidase N, aminopeptidase P, and 5'-nucleotidase activities. Similar results were obtained using human umbilical vein EC-human monocyte and porcine aortic EC-porcine monocyte cocultures. The decrease in ACE activity was monocyte concentration and coculture time dependent, reaching a maximum of 65% decrease in activity at 120 hours. Monocyte-mediated reduction in ACE activity did not require cell to cell contact, since exposure of ECs to conditioned medium from cocultures (CCCM) or from monocyte cultures (MCM) produced a decrease in ACE activity similar to that observed in EC-monocyte cocultures. Exogenously added tumor necrosis factor (TNF)-α and interleukin (IL)-1α, two known secretory products of monocytes, simulated the effects of monocytes on ACE activity. Western blot analysis revealed a decrease in the amount of ACE protein in TNF-α-treated and CCCM-treated ECs compared with control ECs. Both TNF-α and IL-1α were present in CCCM and MCM but not EC- conditioned medium. Incubation of the cocultures with a mixture of neutralizing antibodies against TNF-α and IL-1 totally abolished the monocyte-induced decrease in ACE activity. In conclusion, monocytes decrease ACE activity in cultured ECs through the release of cytokines such as TNF-α and IL-1.

Original languageEnglish (US)
Pages (from-to)512-523
Number of pages12
JournalCirculation Research
Volume79
Issue number3
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • 5'-nucleotidase
  • angiotensin-converting enzyme
  • interleukin-1
  • surface peptidase
  • tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Papapetropoulos, A., Antonov, A., Virmani, R., Kolodgie, F. D., Munn, D. H., Marczin, N., Ryan, J. W., Gerrity, R. G., & Catravas, J. D. (1996). Monocyte- and cytokine-induced downregulation of angiotensin-converting enzyme in cultured human and porcine endothelial cells. Circulation Research, 79(3), 512-523. https://doi.org/10.1161/01.RES.79.3.512