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Interactions between neutrophils and cytokines in blood and alveolar spaces during ARDS
S Chollet-Martin1, B Jourdain, C Gibert
1Laboratoire d'Immunologie et d'Hématologie, Paris, France.
Abstract:
Although the pathogenesis of the acute respiratory distress syndrome (ARDS) is complex and poorly understood, several observations point to an important role of interactions between polymorphonuclear neutrophils (PMN) and cytokines in this process. We therefore studied certain parameters involved in PMN transendothelial migration (adhesion molecule expression and cytoskeletal organization) in patients with ARDS (n = 14) in comparison with other ventilated patients (n = 15). We found that in the basal state, both whole-blood PMN and alveolar PMN obtained by bronchoalveolar lavage (BAL) were activated, as shown by decreased L-selectin CD62L and increased beta 2 integrin CD11b expression, as well as decreased F-actin content. The degree of PMN activation increased with the degree of lung injury and with the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Moreover, the capacity of ex vivo stimulation of alveolar PMN by a bacterial peptide was low in ARDS and could partly account for the high susceptibility of these patients to lung infection. Therefore, ARDS-associated lung injury could be caused, at least in part, by inappropriate adhesion and transendothelial migration of proinflammatory cytokine-primed PMN.
Insights
Polymorphonuclear neutrophils (PMN) are activated in acute respiratory distress syndrome (ARDS), contributing to lung injury. This PMN activation, linked to cytokines, may increase infection susceptibility in ARDS patients.
Area of Science:
- Immunology
- Pulmonology
- Critical Care Medicine
Background:
- Acute respiratory distress syndrome (ARDS) pathogenesis involves complex interactions.
- Polymorphonuclear neutrophils (PMN) and cytokines play a crucial role in ARDS.
- Understanding PMN behavior is key to ARDS pathophysiology.
Purpose of the Study:
- To investigate PMN transendothelial migration parameters in ARDS patients.
- To compare PMN activation in ARDS versus other ventilated patients.
- To correlate PMN activation with lung injury severity and cytokine levels.
Main Methods:
- Studied PMN adhesion molecule expression (CD62L, CD11b) and F-actin content.
- Analyzed whole-blood and bronchoalveolar lavage (BAL) derived PMN from ARDS patients (n=14) and controls (n=15).
- Assessed ex vivo PMN stimulation capacity with bacterial peptides.
Main Results:
- Basal state PMN in ARDS patients showed activation: decreased CD62L, increased CD11b, and reduced F-actin.
- PMN activation correlated with lung injury severity and levels of TNF-alpha, IL-6, and IL-8.
- Alveolar PMN from ARDS patients had impaired response to bacterial peptide stimulation.
Conclusions:
- Inappropriate PMN adhesion and migration, driven by cytokine priming, contribute to ARDS-associated lung injury.
- Activated PMN may increase susceptibility to lung infections in ARDS patients.
- Cytokine-induced PMN dysfunction is a significant factor in ARDS development and progression.