Abstract:
:The biologic effects of endothelin-1 (ET-1) are not limited to its potent vasoconstricting activity. The endothelin receptors, ETA and ETB, have differential tissue and functional distributions. Here we showed that dendritic cells (DCs), the major antigen-presenting cells in the adaptive limb of the immune system, produce large amounts of ET-1 and significantly increase the expression of endothelin receptors upon maturation. Selective blockade of the ETA receptor significantly reduced expression of the mature DC marker CD83, decreased the production of the immunostimulatory cytokine interleukin-12, down-regulated DC ability to stimulate T cells, and promoted DC apoptosis. Selective ETB receptor blockade, on the other hand, resulted in increased expression of CD83 and improved DC survival. Therefore, ET-1/ETA/ETB autocrine/paracrine loops on DCs appear to be essential for the normal maturation and function of human DCs, presenting a unique target for immunomodulatory therapies.
journal_name
Bloodjournal_title
Bloodauthors
Guruli G,Pflug BR,Pecher S,Makarenkova V,Shurin MR,Nelson JBdoi
10.1182/blood-2003-10-3559subject
Has Abstractpub_date
2004-10-01 00:00:00pages
2107-15issue
7eissn
0006-4971issn
1528-0020pii
2003-10-3559journal_volume
104pub_type
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