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Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury in rats
C Delclaux1, S Rezaiguia-Delclaux, C Delacourt
1Institut National de la Santé et de la Recherche Médicale, Unité 296, Hôpital Henri Mondor, Créteil, France.
Abstract:
Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4 and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial partial pressure of O2 (PaO2)/fraction of inspired O2 (FIO2) during mechanical ventilation. The severity of lung injury in the two models was clearly different, since PaO2/FIO2 were approximately 400 mmHg in PYO- and LPS-induced injuries, respectively. Both contrast, alveolar neutrophil influx, unstimulated oxygen metabolite production, and proteinase (elastase, gelatinase B) secretions of ex vivo alveolar PMNs were not larger in the PYO model. Thus the difference in severity was not associated with variations in alveolar neutrophil recruitment or activation. Moreover, gelatinase and leukocyte elastase activities were absent in bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar spaces. We conclude that alveolar neutrophils are not sufficient to create severe respiratory failure.
Insights
Alveolar neutrophils do not cause severe acute lung injury, even when activated. Their presence alone is insufficient to induce respiratory failure in models of acute lung injury.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pathophysiology
Background:
- Polymorphonuclear neutrophils (PMNs) are implicated in adult respiratory distress syndrome pathogenesis.
- Alveolar epithelial barrier integrity is crucial for lung injury progression.
- PMN activity in alveolar spaces may contribute to lung injury.
Purpose of the Study:
- To evaluate alveolar PMN function in rat models of acute lung injury.
- To determine if PMN recruitment and activation correlate with lung injury severity.
- To assess the role of PMNs in causing severe respiratory failure.
Main Methods:
- Induced acute lung injury in rats using endotoxin (LPS) or Pseudomonas aeruginosa (PYO).
- Isolated alveolar PMNs from bronchoalveolar lavage fluid at 4 and 24 hours post-challenge.
- Assessed hypoxemia using the PaO2/FIO2 ratio during mechanical ventilation.
Main Results:
- Lung injury severity differed between PYO and LPS models (PaO2/FIO2 ~400 mmHg).
- Alveolar PMN influx, oxygen metabolite production, and proteinase secretion were similar in both models.
- No significant difference in PMN recruitment or activation was observed despite varying injury severity.
- Gelatinase and elastase activity were absent in bronchoalveolar fluid, indicating effective antiproteinase defenses.
Conclusions:
- Alveolar neutrophils are not sufficient to cause severe respiratory failure.
- The severity of acute lung injury is not solely dependent on alveolar neutrophil recruitment or activation.
- Effective antiproteinase mechanisms in the alveolar space may limit PMN-induced lung damage.