Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium

Abstract Endothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were...

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Autores principales:	Nadzeya Marozkina, Laura Smith, Yi Zhao, Joe Zein, James F. Chmiel, Jeeho Kim, Janna Kiselar, Michael D. Davis, Rebekah S. Cunningham, Scott H. Randell, Benjamin Gaston
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c3588f16218844d884b6e71832474325
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spelling	oai:doaj.org-article:c3588f16218844d884b6e718324743252021-12-02T18:46:54ZSomatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium10.1038/s41598-021-94782-52045-2322https://doaj.org/article/c3588f16218844d884b6e718324743252021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94782-5https://doaj.org/toc/2045-2322Abstract Endothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.Nadzeya MarozkinaLaura SmithYi ZhaoJoe ZeinJames F. ChmielJeeho KimJanna KiselarMichael D. DavisRebekah S. CunninghamScott H. RandellBenjamin GastonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadzeya Marozkina Laura Smith Yi Zhao Joe Zein James F. Chmiel Jeeho Kim Janna Kiselar Michael D. Davis Rebekah S. Cunningham Scott H. Randell Benjamin Gaston Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
description	Abstract Endothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.
format	article
author	Nadzeya Marozkina Laura Smith Yi Zhao Joe Zein James F. Chmiel Jeeho Kim Janna Kiselar Michael D. Davis Rebekah S. Cunningham Scott H. Randell Benjamin Gaston
author_facet	Nadzeya Marozkina Laura Smith Yi Zhao Joe Zein James F. Chmiel Jeeho Kim Janna Kiselar Michael D. Davis Rebekah S. Cunningham Scott H. Randell Benjamin Gaston
author_sort	Nadzeya Marozkina
title	Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
title_short	Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
title_full	Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
title_fullStr	Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
title_full_unstemmed	Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
title_sort	somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c3588f16218844d884b6e71832474325
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Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium

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