title: Different changes in mitochondrial apoptotic pathway in lymphocytes and granulocytes in cirrhotic patients with sepsis.
abstract: OBJECTIVE
  Apoptosis regulates leucocyte response during bacterial infections. This study explored leucocyte apoptotic pathway in cirrhotic patients with or without infections or sepsis.
  
  
  METHODS
  In cirrhotic patients with bacterial infection or sepsis, the expression of Caspase 9, Bcl-2 family proteins, which comprises pro-apoptotic molecules, such as Bax, and anti-apoptotic molecules, such as Bcl-2 and Bcl-xL, were measured in peripheral lymphocytes and granulocytes. Regulatory microRNAs MIR-15 and MIR-16 were also measured.
  
  
  RESULTS
  This study enrolled 80 patients with cirrhosis, of whom 28 had no evidence of infections, 32 had bacterial infections and 20 had sepsis; reference values were obtained from 10 age-matched healthy subjects. An over-expression of Caspase-9 and pro-apoptotic protein Bax was found in lymphocytes of cirrhotic patients with infection or sepsis as compared with non-infected cases (P = 0.05 and 0.0001, respectively), while anti-apoptotic proteins Bcl-2 and Bcl-xL were downregulated. In granulocytes, lowest expression of pro-apoptotic protein Bax occurred in septic patients, while in cirrhotics with infections anti-apoptotic Bcl-2 and Bcl-xL were upregulated. Eight patients died; the survivors had less derangements in Bax, Bcl-2 and BcL-xL expression than non-survivors. The pro-apoptotic miRNA, MIR-15 and MIR-16, were upregulated in cirrhotics with bacterial infections.
  
  
  CONCLUSIONS
  Overall, the data show in lymphocytes, and not in granulocytes, an activation of the pro-apoptotic pathway in cirrhotic patients with bacterial infections, which correlates with the severity of the infection and the outcome.
authors.affiliation: Department of Internal and Specialistic Medicine, Infectious Diseases and Viral Hepatitis Unit, Second University of Naples, Naples, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Precone
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Stornaiuolo
authors.forename: Annamaria
authors.initials: A
authors.lastname: Amato
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Brancaccio
authors.forename: Salvatore
authors.initials: S
authors.lastname: Nardiello
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Gaeta
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000097:blood*; D001424:Bacterial Infections / Q000097:blood* / Q000235:genetics / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006098:Granulocytes / Q000737:chemistry* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000235:genetics / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry* / Q000382:microbiology / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood; D008875:Middle Aged; D008928:Mitochondria / Q000737:chemistry* / Q000382:microbiology / Q000473:pathology; D011379:Prognosis; D018805:Sepsis / Q000097:blood* / Q000235:genetics / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs