title: Apoptosis in cells of bronchoalveolar lavage: a cellular reaction in patients who die with sepsis and respiratory failure.
abstract: OBJECTIVE
  Apoptosis represents a physiologic clearance mechanism in human tissues. The role of apoptosis has not been examined in lung cell populations, such as alveolar macrophages of septic patients, an organ frequently insulted in these patients. This study was designed to examine the effect of sepsis on the apoptosis of alveolar macrophages.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Intensive care unit and surgical intensive care and trauma unit of a large university hospital in Athens, Greece.
  
  
  METHODS
  Bronchoalveolar lavage was obtained from 20 consecutive patients who met the criteria for sepsis, admitted to two intensive care units. Bronchoalveolar lavage was obtained from nine volunteers without lung disease who served as controls.
  
  
  METHODS
  None.
  
  
  RESULTS
  The specimens were analyzed by using annexin V binding, terminal deoxynucleotidyl transfer-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL), DNA laddering, light microscopy, and immunohistochemistry. Spontaneous apoptosis of bronchoalveolar lavage cells and particularly of alveolar macrophages was significantly decreased in septic patients compared with nonseptic controls. This finding was confirmed by using morphologic criteria and the TUNEL method. Furthermore, gel electrophoresis of DNA obtained from bronchoalveolar cells revealed that DNA fragmentation was not necessarily associated with apoptotic cell death. The bcl-2 gene was minimally expressed in the control group. An inverse correlation was found between the percentage of apoptotic alveolar macrophages and the severity of sepsis.
  
  
  CONCLUSIONS
  The prolonged survival of lung cells in septic patients and especially of alveolar macrophages may be attributable to the inhibition of apoptosis. This seems to represent an initial attempt of the host to increase the defense capacity to kill the invading microorganism, resulting in an unbalanced tissue load of cells and an uncontrolled release of toxic metabolites. Furthermore, the inhibition of apoptosis in septic patients may explain why lung function is impaired, leading to sepsis-induced acute respiratory distress syndrome and death.
authors.affiliation: Laboratory of Surgical Research, Athens University Medical School, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Liacos
authors.forename: S
authors.initials: S
authors.lastname: Katsaragakis
authors.forename: M M
authors.initials: MM
authors.lastname: Konstadoulakis
authors.forename: E G
authors.initials: EG
authors.lastname: Messaris
authors.forename: M
authors.initials: M
authors.lastname: Papanicolaou
authors.forename: G G
authors.initials: GG
authors.lastname: Georgiadis
authors.forename: E
authors.initials: E
authors.lastname: Menenakos
authors.forename: A
authors.initials: A
authors.lastname: Vasiliadi-Chioti
authors.forename: G
authors.initials: G
authors.lastname: Androulakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D053938:DNA Fragmentation; D005260:Female; D019254:Genes, bcl-2; D006115:Greece / Q000453:epidemiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000276:immunology* / Q000401:mortality; D018805:Sepsis / Q000276:immunology* / Q000401:mortality; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D017304:Annexin A5