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Int. J. Mol. Sci. 2015, 16(5), 11196-11212; doi:10.3390/ijms160511196

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

1
Department of General, Visceral, Vascular and Thoracic Surgery, Charité Universitätsmedizin, Campus Mitte, 10117 Berlin, Germany
2
Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA
3
The Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48202, USA
4
Caris Life Sciences, Phoenix, AZ 85040, USA
5
Department of Surgery, Temple University School of Medicine, Philadelphia, PA 19140, USA
Current affiliation: Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48202, USA.
Current affiliation: Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
*
Author to whom correspondence should be addressed.
Academic Editors: Jonathan Golledge and Joseph V. Moxon
Received: 20 November 2014 / Revised: 26 January 2015 / Accepted: 28 January 2015 / Published: 18 May 2015
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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Abstract

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. View Full-Text
Keywords: human aorta; immunohistochemistry; double-staining; AAA; aortic aneurysm human aorta; immunohistochemistry; double-staining; AAA; aortic aneurysm
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hinterseher, I.; Schworer, C.M.; Lillvis, J.H.; Stahl, E.; Erdman, R.; Gatalica, Z.; Tromp, G.; Kuivaniemi, H. Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms. Int. J. Mol. Sci. 2015, 16, 11196-11212.

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