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Neutrophil apoptosis in the acute respiratory distress syndrome
G Matute-Bello1, W C Liles, F Radella
1Section of Pulmonary and Critical Care Medicine, Harborview Medical Center, Seattle, Washington, USA.
Abstract:
Little is known about neutrophil (PMN) apoptosis in the acute respiratory distress syndrome (ARDS). We uses morphologic criteria to count apoptotic PMN in bronchoalveolar lavage fluid (BAL) of 35 patients on Days 1, 3, 7, 14, and 21 of ARDS and 13 patients on Days 1 and 3 of risk for ARDS. We found that the proportion of apoptotic PMN in BAL was low throughout the course of ARDS. There was no significant difference between the percentage of apoptotic PMN in patients at risk and patients with established ARDS or between patients who lived (2.4%) and patients who died (1.8%). When normal human PMN were incubated in ARDS BAL, a significantly lower proportion became apoptotic (50 +/- 4%), as compared with PMN incubated in lavage fluid from normal volunteers (76 +/- 7%, p < 0.05). This antiapoptotic effect of ARDS BAL was blocked by immunodepleting BAL of G-CSF and GM-CSF. We conclude that the proportion of apoptotic PMN recovered from the lungs of patients with ARDS is low throughout the course of ARD S. Furthermore, BAL from patients with ARDS prolongs survival of normal human PMN in vitro, and this effect is partially mediated by G-CSF and GM-CSF.
Insights
Neutrophil apoptosis is low in acute respiratory distress syndrome (ARDS) lungs. ARDS bronchoalveolar lavage fluid (BAL) inhibits normal neutrophil apoptosis, partly due to G-CSF and GM-CSF.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Neutrophil apoptosis is crucial for resolving inflammation.
- The role of neutrophil apoptosis in acute respiratory distress syndrome (ARDS) remains unclear.
- Understanding neutrophil behavior in ARDS is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the proportion of apoptotic neutrophils in bronchoalveolar lavage fluid (BAL) during ARDS.
- To determine if ARDS BAL fluid affects normal neutrophil apoptosis.
- To identify factors in ARDS BAL fluid contributing to altered neutrophil apoptosis.
Main Methods:
- Morphological assessment of apoptotic neutrophils in BAL from ARDS patients and at-risk individuals.
- In vitro incubation of normal human neutrophils with ARDS BAL fluid and control BAL fluid.
- Immunodepletion of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) from ARDS BAL fluid.
Main Results:
- The proportion of apoptotic neutrophils in BAL fluid was low throughout the course of ARDS.
- No significant difference in apoptotic neutrophil percentage was observed between at-risk and ARDS patients, or between survivors and non-survivors.
- ARDS BAL fluid significantly reduced the apoptosis of normal human neutrophils compared to control fluid (50% vs. 76%).
- The antiapoptotic effect of ARDS BAL fluid was partially blocked by removing G-CSF and GM-CSF.
Conclusions:
- Neutrophil apoptosis is suppressed in the lungs of ARDS patients.
- ARDS bronchoalveolar lavage fluid exhibits an antiapoptotic effect on normal neutrophils.
- G-CSF and GM-CSF partially mediate the survival-prolonging effect of ARDS BAL fluid on neutrophils.