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

International Journal of Molecular Sciences

Irene Hinterseher¹  Charles M. Schworer⁵  John H. Lillvis⁴  Elizabeth Stahl⁵  Robert Erdman⁵  Zoran Gatalica²  Gerard Tromp⁵  Helena Kuivaniemi⁵  Jonathan Golledge³ 

[1] Department of General, Visceral, Vascular and Thoracic Surgery, Charité Universitätsmedizin, Campus Mitte, 10117 Berlin, Germany; E-Mail:;Caris Life Sciences, Phoenix, AZ 85040, USA; E-Mail:;Department of General, Visceral, Vascular and Thoracic Surgery, Charité Universitätsmedizin, Campus Mitte, 10117 Berlin, Germany; E-Mail;The Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48202, USA; E-Mail:;Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA; E-Mails:

关键词: human aorta;    immunohistochemistry;    double-staining;    AAA;    aortic aneurysm;   

DOI  :  10.3390/ijms160511196

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.