title: Impaired Fas-induced apoptosis of T lymphocytes in patients with abdominal aortic aneurysms.
abstract: OBJECTIVE
  Homeostasis of the immune system is maintained by apoptotic elimination of potentially pathogenic autoreactive lymphocytes. Emerging evidence shows that Fas-mediated apoptosis is impaired in activated lymphocytes from patients with autoimmune disease. The aim of this work was to assess apoptosis mediated by the cell death receptor Fas in peripheral T lymphocytes from patients with abdominal aortic aneurysms (AAA).
  
  
  METHODS
  The apoptotic pathway was triggered by anti-Fas monoclonal antibodies in cultured and activated peripheral T-cell lines from 20 AAA patients with control groups of 15 patients with aortic atherosclerotic occlusive disease (AOD) and 25 healthy individuals. Cell survival and death (apoptosis) rate were assessed.
  
  
  RESULTS
  Cross-linkage of Fas receptor exerted a strong apoptotic response on T cells from AOD patients and healthy controls, but a much less pronounced effect on T cells from AAA patients. The evaluation of cell survival rate showed a significantly higher percentage in AAA group (98.9% +/- 10.3%) than in the AOD subjects (58.9% +/- 15.2%) or the healthy group (59.4% +/- 12.9%; P < .001). Apoptosis assessment by annexin V and propidium iodide staining and flow cytometry showed similar results. The defect in AAA group was not due to decreased Fas expression, since Fas was expressed at normal levels. Moreover, it specifically involved the Fas system because cell death was induced in the normal way by methylprednisolone. Complementary DNA sequencing identified no causal Fas gene mutation, but two silent single nucleotide polymorphisms with higher frequency were found in the AAA group.
  
  
  CONCLUSIONS
  Fas-induced apoptosis in activated T cells from AAA patients is impaired. This may disturb the normal down-regulation of the immune response and thus provide a new insight into possible mechanisms and routes in the pathogenesis of AAA.
authors.affiliation: Third General Surgery Department, First Affiliated Hospital, China Medical University, Shenyang, China. jianzhang_cmu@yahoo.com.cn <jianzhang_cmu@yahoo.com.cn>
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Dittmar
authors.initials: D
authors.lastname: Böckler
authors.forename: Eduard
authors.initials: E
authors.lastname: Ryschich
authors.forename: Klaus
authors.initials: K
authors.lastname: Klemm
authors.forename: Hardy
authors.initials: H
authors.lastname: Schumacher
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Jens R
authors.initials: JR
authors.lastname: Allenberg
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology* / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C491901:FAS protein, human; D005938:Glucocorticoids; C064769:N-acetylsphingosine; C411023:anti-Fas monoclonal antibody; D019014:fas Receptor; D013110:Sphingosine; D008775:Methylprednisolone