title: Immunohistochemical analysis of the natural killer cell cytotoxicity pathway in human abdominal aortic aneurysms.
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.
authors.affiliation: Department of General, Visceral, Vascular and Thoracic Surgery, Charité Universitätsmedizin, Campus Mitte, 10117 Berlin, Germany. irene.hinterseher@charite.de.
authors.forename: Irene
authors.initials: I
authors.lastname: Hinterseher
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. cmschworer@gmail.com.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Schworer
authors.affiliation: The Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48202, USA. johnlillvis@gmail.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Lillvis
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. ecs40@pitt.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stahl
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. rerdman@geisinger.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Erdman
authors.affiliation: Caris Life Sciences, Phoenix, AZ 85040, USA. zgatalica@carisls.com.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. gctromp@geisinger.edu.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. shkuivaniemi@geisinger.edu.|Department of Surgery, Temple University School of Medicine, Philadelphia, PA 19140, USA. shkuivaniemi@geisinger.edu.
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D051966:Phospholipase C gamma / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D000097382:CD68 Molecule
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016827:CD8 Antigens; D051418:Focal Adhesion Kinase 2; D008565:Membrane Proteins; D051966:Phospholipase C gamma; D051567:Proto-Oncogene Proteins c-vav; D011971:Receptors, Immunologic; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C120528:HCST protein, human; C110546:TYROBP protein, human; C496618:VAV1 protein, human; C496621:VAV3 protein, human; C103547:PTK2B protein, human
keywords: AAA; aortic aneurysm; double-staining; human aorta; immunohistochemistry