Apoptosis in bronchoalveolar cells represents a major pathophysiologic pathway of death in septic patients

C. Liacos, M. M. Konstadoulakis, S. Katsaragakis, E. Messaris, M. Papanicolaou, G. Georgiadis, E. Menekakos, A. Margiolis, G. Androulakis

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE. Apoptosis represents a physiological clearance mechanism in human tissues. The role of apoptosis has not been examined in lung cell populations of septic patients, although the lung is frequently affected in these patients. This study was designed to examine the effect of sepsis on the apoptosis of bronchoalveolar cells and macrophages. METHOD. Bronchoalveolar lavage (BAL) was obtained from 20 consecutive patients, admitted to two intensive care units, who met the criteria for sepsis. BAL from 9 volunteers without lung disease served as controls. The specimens were analyzed using annexin V binding, terminal deoxynucleotidyl transferase mediated dUTP nick end ladeling (TUNEL), DNA laddering, light microscopy and the expression of the bcl-2 gene. RESULTS. Spontaneous apoptosis of BAL cells and particularly of alveolar macrophages was significantly decreased in septic patients compared to the non-septic volunteers (P<0.01). This finding was confirmed using morphologic criteria and the TUNEL method. 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 significantly (P<0.01) over-expressed in the control group. CONCLUSIONS. The prolonged survival of lung cells in septic patients and especially of alveolar macrophages is due to the inhibition of apoptosis. This represents an initial attempt of the host to increase the defensive capacity for killing invading microorganisms resulting in an imbalanced tissue load inhibition of cells and an uncontrolled release of toxic metabolites. Apoptosis inhibition may in this way explain the destruction of the lung architecture and function which leads to sepsis-induced acute respiratory distress syndrome and death.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalArchives of Hellenic Medicine
Volume17
Issue number2
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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