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Apoptosis in cells of bronchoalveolar lavage: A cellular reaction in patients who die with sepsis and respiratory failure

Liacos, Christine PhD; Katsaragakis, Stylianos MD, PhD; Konstadoulakis, Manousos M. MD, PhD; Messaris, Evangelos G. MD; Papanicolaou, Metaxia MD; Georgiadis, George G. MD; Menenakos, Evangelos MD; Vasiliadi-Chioti, Athanasia; Androulakis, George MD, PhD, FACS

CLINICAL INVESTIGATIONS
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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.

Design  Prospective study.

Setting  Intensive care unit and surgical intensive care and trauma unit of a large university hospital in Athens, Greece.

Patients  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.

Interventions  None.

Measurements and Main 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.

From the Laboratory of Surgical Research (CL, MMK, EGM, GA) and the Surgical Intensive Care and Trauma Unit (SK, MMK, GA) of the First Department of Propaedeutic Surgery, Athens University Medical School; the Intensive Care Unit (MP, GGG) of the Hippocration Hospital, Athens, Greece; and the Department of Immunology (AV-C) of the Elena Venizelou Hospital, Athens, Greece.

Supported, in part, by a grant (to MMK) from the University of Athens Special Account for Research Grants.

Address requests for reprints to Manousos M. Konstadoulakis, MD, PhD, Kalvou 24, P. Psychico, 154 52, Athens, Greece. E-mail: labsures@med.uoa.gr

The inhibition of apoptosis in septic patients may explain why lung function is impaired, leading to sepsis-induced acute respiratory distress syndrome and death.

© 2001 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins