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Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody

Resistin and resistin-like molecules are pleiotropic cytokines that are involved in inflammatory diseases. Our previous work suggested that resistin has the potential to be used as a biomarker and therapeutic target for human pulmonary arterial hypertension. However, data are limited on the distribu...

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Autores principales: Lin, Qing, Price, Shari A., Skinner, John T., Hu, Bin, Fan, Chunling, Yamaji-Kegan, Kazuyo, Johns, Roger A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329134/
https://www.ncbi.nlm.nih.gov/pubmed/32609743
http://dx.doi.org/10.1371/journal.pone.0235546
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author Lin, Qing
Price, Shari A.
Skinner, John T.
Hu, Bin
Fan, Chunling
Yamaji-Kegan, Kazuyo
Johns, Roger A.
author_facet Lin, Qing
Price, Shari A.
Skinner, John T.
Hu, Bin
Fan, Chunling
Yamaji-Kegan, Kazuyo
Johns, Roger A.
author_sort Lin, Qing
collection PubMed
description Resistin and resistin-like molecules are pleiotropic cytokines that are involved in inflammatory diseases. Our previous work suggested that resistin has the potential to be used as a biomarker and therapeutic target for human pulmonary arterial hypertension. However, data are limited on the distribution of resistin in healthy human organs. In this study, we used our newly developed anti-human resistin (hResistin) antibody to immunohistochemically detect the expression, localization, and intracellular/extracellular compartmentalization of hResistin in a full human tissue panel from healthy individuals. The potential cross reactivity of this monoclonal anti-hResistin IgG1 with normal human tissues also was verified. Results showed that hResistin is broadly distributed and principally localized in the cytoplasmic granules of macrophages scattered in the interstitium of most human tissues. Bone marrow hematopoietic precursor cells also exhibited hResistin signals in their cytoplasmic granules. Additionally, hResistin labeling was observed in the cytoplasm of nervous system cells. Notably, the cytokine activity of hResistin was illustrated by positively stained extracellular material in most human tissues. These data indicate that our generated antibody binds to the secreted hResistin and support its potential use for immunotherapy to reduce circulating hResistin levels in human disease. Our findings comprehensively document the basal expression patterns of hResistin protein in normal human tissues, suggest a critical role of this cytokine in normal and pathophysiologic inflammatory processes, and offer key insights for using our antibody in future pharmacokinetic studies and immunotherapeutic strategies.
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spelling pubmed-73291342020-07-14 Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody Lin, Qing Price, Shari A. Skinner, John T. Hu, Bin Fan, Chunling Yamaji-Kegan, Kazuyo Johns, Roger A. PLoS One Research Article Resistin and resistin-like molecules are pleiotropic cytokines that are involved in inflammatory diseases. Our previous work suggested that resistin has the potential to be used as a biomarker and therapeutic target for human pulmonary arterial hypertension. However, data are limited on the distribution of resistin in healthy human organs. In this study, we used our newly developed anti-human resistin (hResistin) antibody to immunohistochemically detect the expression, localization, and intracellular/extracellular compartmentalization of hResistin in a full human tissue panel from healthy individuals. The potential cross reactivity of this monoclonal anti-hResistin IgG1 with normal human tissues also was verified. Results showed that hResistin is broadly distributed and principally localized in the cytoplasmic granules of macrophages scattered in the interstitium of most human tissues. Bone marrow hematopoietic precursor cells also exhibited hResistin signals in their cytoplasmic granules. Additionally, hResistin labeling was observed in the cytoplasm of nervous system cells. Notably, the cytokine activity of hResistin was illustrated by positively stained extracellular material in most human tissues. These data indicate that our generated antibody binds to the secreted hResistin and support its potential use for immunotherapy to reduce circulating hResistin levels in human disease. Our findings comprehensively document the basal expression patterns of hResistin protein in normal human tissues, suggest a critical role of this cytokine in normal and pathophysiologic inflammatory processes, and offer key insights for using our antibody in future pharmacokinetic studies and immunotherapeutic strategies. Public Library of Science 2020-07-01 /pmc/articles/PMC7329134/ /pubmed/32609743 http://dx.doi.org/10.1371/journal.pone.0235546 Text en © 2020 Lin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lin, Qing
Price, Shari A.
Skinner, John T.
Hu, Bin
Fan, Chunling
Yamaji-Kegan, Kazuyo
Johns, Roger A.
Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody
title Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody
title_full Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody
title_fullStr Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody
title_full_unstemmed Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody
title_short Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody
title_sort systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329134/
https://www.ncbi.nlm.nih.gov/pubmed/32609743
http://dx.doi.org/10.1371/journal.pone.0235546
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