title: Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis.
abstract: Reduced mitochondrial membrane potential (Delta(Psi)m), which is considered as an initial and irreversible step towards apoptosis, as well as cell death regulating proteins, such as Fas, Hsp70, or Bcl-2, may play an important role in sepsis. We studied the relationship between sepsis severity and peripheral blood monocyte Delta(Psi)m, cell death (necrosis and apoptosis), soluble Fas ligand, Hsp70, and Bcl-2 expression over time in 18 patients with sepsis, and compared these data with those of a group of 17 healthy control subjects. All measurements were performed within 3 d of the onset of severe sepsis (T1), then 7 to 10 d later (T2), and finally at hospital discharge (T3). Delta(Psi)m was expressed as the percent monocytes with altered Delta(Psi)m (%Delta(Psi)m). Patients with sepsis had greater %Delta(Psi)m at T1 and T2 but not at T3 (14.6 +/- 2.6% and 15.9 +/- 2%, respectively, versus control 6.6 +/- 0.2%, p < 0.01). Septic patients exhibited greater cell death in their monocytes and had greater Hsp70 expression only at T1. Bcl-2 levels were similar in septic and control subjects. Comparing survivors with non-survivors of sepsis, nonsurvivors had a greater %Delta(Psi)m at T1 (26.4 +/- 5.3% versus 10.1 +/- 2.7%, p < 0.01) and a significant decrease in Bcl-2 expression, whereas no difference was found in Hsp70 levels. These results indicate that mitochondrial dysfunction and subsequent cell death occur in severe sepsis and suggest that %Delta(Psi)m is a marker of severity in human sepsis.
  
  
  BACKGROUND
  mitochondria; apoptosis; sepsis; heat-shock protein 70; proto-oncogene protein c-Bcl-2
authors.affiliation: Laboratory of Respiratory Physiology and Medical Intensive Care Unit, APHP, Cochin Port-Royal Hospital, Paris, France. christophe.adrie@wanadoo.fr
authors.forename: C
authors.initials: C
authors.lastname: Adrie
authors.forename: M
authors.initials: M
authors.lastname: Bachelet
authors.forename: M
authors.initials: M
authors.lastname: Vayssier-Taussat
authors.forename: F
authors.initials: F
authors.lastname: Russo-Marie
authors.forename: I
authors.initials: I
authors.lastname: Bouchaert
authors.forename: M
authors.initials: M
authors.lastname: Adib-Conquy
authors.forename: J M
authors.initials: JM
authors.lastname: Cavaillon
authors.forename: M R
authors.initials: MR
authors.lastname: Pinsky
authors.forename: J F
authors.initials: JF
authors.lastname: Dhainaut
authors.forename: B S
authors.initials: BS
authors.lastname: Polla
mesh_terms: D000368:Aged; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D009336:Necrosis; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D018805:Sepsis / Q000150:complications / Q000503:physiopathology*; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D018840:HSP70 Heat-Shock Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2