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Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms

Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohist...

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Autores principales: Hinterseher, Irene, Schworer, Charles M., Lillvis, John H., Stahl, Elizabeth, Erdman, Robert, Gatalica, Zoran, Tromp, Gerard, Kuivaniemi, Helena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463696/
https://www.ncbi.nlm.nih.gov/pubmed/25993291
http://dx.doi.org/10.3390/ijms160511196
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author Hinterseher, Irene
Schworer, Charles M.
Lillvis, John H.
Stahl, Elizabeth
Erdman, Robert
Gatalica, Zoran
Tromp, Gerard
Kuivaniemi, Helena
author_facet Hinterseher, Irene
Schworer, Charles M.
Lillvis, John H.
Stahl, Elizabeth
Erdman, Robert
Gatalica, Zoran
Tromp, Gerard
Kuivaniemi, Helena
author_sort Hinterseher, Irene
collection PubMed
description Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against nine members of the NK pathway (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from AAA repair operations (n = 6) and control aortae (n = 8) from age-, sex- and ethnicity-matched donors from autopsies. The results confirmed the microarray results. Two different members of the NK pathway, HCST and GRZB, which act at different steps in the NK-pathway, were actively transcribed and translated into proteins in the same cells in the AAA tissue demonstrated by double staining. Furthermore, double staining with antibodies against CD68 or CD8 together with HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed proteins of the NK-pathway but were not the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide strong evidence that the NK Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight for future studies to dissect the pathogenesis of human AAA.
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spelling pubmed-44636962015-06-16 Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms Hinterseher, Irene Schworer, Charles M. Lillvis, John H. Stahl, Elizabeth Erdman, Robert Gatalica, Zoran Tromp, Gerard Kuivaniemi, Helena Int J Mol Sci Article Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against nine members of the NK pathway (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from AAA repair operations (n = 6) and control aortae (n = 8) from age-, sex- and ethnicity-matched donors from autopsies. The results confirmed the microarray results. Two different members of the NK pathway, HCST and GRZB, which act at different steps in the NK-pathway, were actively transcribed and translated into proteins in the same cells in the AAA tissue demonstrated by double staining. Furthermore, double staining with antibodies against CD68 or CD8 together with HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed proteins of the NK-pathway but were not the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide strong evidence that the NK Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight for future studies to dissect the pathogenesis of human AAA. MDPI 2015-05-18 /pmc/articles/PMC4463696/ /pubmed/25993291 http://dx.doi.org/10.3390/ijms160511196 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hinterseher, Irene
Schworer, Charles M.
Lillvis, John H.
Stahl, Elizabeth
Erdman, Robert
Gatalica, Zoran
Tromp, Gerard
Kuivaniemi, Helena
Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
title Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
title_full Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
title_fullStr Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
title_full_unstemmed Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
title_short Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
title_sort immunohistochemical analysis of the natural killer cell cytotoxicity pathway in human abdominal aortic aneurysms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463696/
https://www.ncbi.nlm.nih.gov/pubmed/25993291
http://dx.doi.org/10.3390/ijms160511196
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