Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops

Georgi Guruli, Beth Pflug, Stefana Pecher, Valeria Makarenkova, Michael R. Shurin, Joel B. Nelson

Research output: Contribution to journalArticle

41 Citations (Scopus)

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/ET A/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.

Original languageEnglish (US)
Pages (from-to)2107-2115
Number of pages9
JournalBlood
Volume104
Issue number7
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Endothelin A Receptors
Endothelin Receptors
Dendritic Cells
Endothelin-1
T-cells
Immunomodulation
Immune system
Antigen-Presenting Cells
Tissue Distribution
Interleukin-12
Immune System
Cell Survival
Extremities
Tissue
Apoptosis
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops. / Guruli, Georgi; Pflug, Beth; Pecher, Stefana; Makarenkova, Valeria; Shurin, Michael R.; Nelson, Joel B.

In: Blood, Vol. 104, No. 7, 01.10.2004, p. 2107-2115.

Research output: Contribution to journalArticle

Guruli, Georgi ; Pflug, Beth ; Pecher, Stefana ; Makarenkova, Valeria ; Shurin, Michael R. ; Nelson, Joel B. / Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops. In: Blood. 2004 ; Vol. 104, No. 7. pp. 2107-2115.
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AU - Shurin, Michael R.

AU - Nelson, Joel B.

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