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Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide

Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is...

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Autores principales: Lai, Thung-S., Lindberg, Robert A., Zhou, Hua-Lin, Haroon, Zishan A., Dewhirst, Mark W., Hausladen, Alfred, Juang, Y.-L., Stamler, Jonathan S., Greenberg, Charles S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701052/
https://www.ncbi.nlm.nih.gov/pubmed/29170410
http://dx.doi.org/10.1038/s41598-017-16342-0
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author Lai, Thung-S.
Lindberg, Robert A.
Zhou, Hua-Lin
Haroon, Zishan A.
Dewhirst, Mark W.
Hausladen, Alfred
Juang, Y.-L.
Stamler, Jonathan S.
Greenberg, Charles S.
author_facet Lai, Thung-S.
Lindberg, Robert A.
Zhou, Hua-Lin
Haroon, Zishan A.
Dewhirst, Mark W.
Hausladen, Alfred
Juang, Y.-L.
Stamler, Jonathan S.
Greenberg, Charles S.
author_sort Lai, Thung-S.
collection PubMed
description Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is largely unknown. Here we show that on endothelial surfaces, NO is associated with the sulfhydryl-rich protein tissue transglutaminase (TG2), thereby endowing the membrane surfaces with anti-inflammatory properties. We find that tumor necrosis factor-α-stimulated neutrophil adherence is opposed by TG2 molecules that are bound to the endothelial surface. Alkylation of cysteine residues in TG2 or inhibition of endothelial NO synthesis renders the surface-bound TG2 inactive, whereas specific, high affinity binding of S-nitrosylated TG2 (SNO-TG2) to endothelial surfaces restores the anti-inflammatory properties of the endothelium, and reconstitutes the activity of endothelial-derived NO. We also show that SNO-TG2 is present in healthy tissues and that it forms on the membranes of shear-activated endothelial cells. Thus, the anti-inflammatory mechanism that prevents neutrophils from adhering to endothelial cells is identified with TG2 S-nitrosylation at the endothelial cell-blood interface.
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spelling pubmed-57010522017-11-30 Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide Lai, Thung-S. Lindberg, Robert A. Zhou, Hua-Lin Haroon, Zishan A. Dewhirst, Mark W. Hausladen, Alfred Juang, Y.-L. Stamler, Jonathan S. Greenberg, Charles S. Sci Rep Article Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is largely unknown. Here we show that on endothelial surfaces, NO is associated with the sulfhydryl-rich protein tissue transglutaminase (TG2), thereby endowing the membrane surfaces with anti-inflammatory properties. We find that tumor necrosis factor-α-stimulated neutrophil adherence is opposed by TG2 molecules that are bound to the endothelial surface. Alkylation of cysteine residues in TG2 or inhibition of endothelial NO synthesis renders the surface-bound TG2 inactive, whereas specific, high affinity binding of S-nitrosylated TG2 (SNO-TG2) to endothelial surfaces restores the anti-inflammatory properties of the endothelium, and reconstitutes the activity of endothelial-derived NO. We also show that SNO-TG2 is present in healthy tissues and that it forms on the membranes of shear-activated endothelial cells. Thus, the anti-inflammatory mechanism that prevents neutrophils from adhering to endothelial cells is identified with TG2 S-nitrosylation at the endothelial cell-blood interface. Nature Publishing Group UK 2017-11-23 /pmc/articles/PMC5701052/ /pubmed/29170410 http://dx.doi.org/10.1038/s41598-017-16342-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lai, Thung-S.
Lindberg, Robert A.
Zhou, Hua-Lin
Haroon, Zishan A.
Dewhirst, Mark W.
Hausladen, Alfred
Juang, Y.-L.
Stamler, Jonathan S.
Greenberg, Charles S.
Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
title Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
title_full Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
title_fullStr Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
title_full_unstemmed Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
title_short Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
title_sort endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701052/
https://www.ncbi.nlm.nih.gov/pubmed/29170410
http://dx.doi.org/10.1038/s41598-017-16342-0
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