In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. 3 ( 1996-09), p. 512-523
Abstract:
We investigated the effects of monocytes on endothelial cell (EC) ectoenzyme activity. Coculture of human aortic ECs with human monocytes (2×10 5 monocytes per 2-cm 2 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.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.79.3.512
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1996
detail.hit.zdb_id:
1467838-X
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