Neutrophil Apoptosis in the Acute Respiratory Distress Syndrome

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.

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

“…The concentrations of G-CSF in BAL fluid during the first week of injury (median (range) 240 pg . mL -1 (11±1,000)) are similar to those reported in the previous study on the first day after the onset of injury [11]. Initial levels for the total group of patients were significantly higher in nonsurvivors than survivors (p<0.05).…”

“…There has been one previous study of G-CSF levels in BAL fluid from patients with ARDS [11]. They were on average 10-fold higher than those in BAL from normal volunteers (median (range) 238 pg .…”

“…These findings alone are difficult to interpret because apoptotic cells are rarely detected in vivo due to their very rapid clearance by phagocytes [16]. More importantly, BAL fluid from their patients with ARDS reduced the rate of apoptosis of blood neutrophils in vitro [11]. Furthermore, the anti-apoptotic effect could be blocked by preincubating BAL fluids with polyclonal antibodies directed against G-CSF and GM-CSF, indicating that both cytokines may prolong the survival of neutrophils in the lungs of patients with ARDS.…”

“…Circulating neutrophils have a short life span of 6±8 h due to programmed cell death, "apoptosis", which normally ensures that the effete cells are recognized and cleared by phagocytes and other cells without spilling their potentially toxic contents [10]. Recent morphological evidence suggests that apoptosis of neutrophils is suppressed during the course of ARDS [11]. Furthermore, BAL fluid from the same patients prolonged the life span of normal neutrophils in vitro.…”

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

“…In hyperoxic lungs, activation of NF-κB is detected in multiple cell types, such as alveolar macrophages, epithelial lung cells, human pulmonary artery endothelial cells and the monocytic THP-1 cell line [16,45,70,[72][73][74][75][76][77][78]. In addition, hyperoxia can also potentiate LPS and IFN-γ induced NF-κB activation [72].…”