Abstract

<b>Background:</b> Acute respiratory distress syndrome (ARDS) is a life-threating lung condition resulting from a direct and indirect injury to the lungs. Pathophysiologically it is characterized by an acute alveolar damage, an increased permeability of the microvascular-barrier, leading to protein-rich pulmonary edema and subsequent impairment of arterial oxygenation and respiratory failure. This study examined the role of extracellular ATP in recruiting inflammatory cells to the lung after induction of acute lung injury with lipopolysaccharide (LPS). <b>Methods and Results:</b> To address this hypothesis, we used a murine(C57/Bl6 mice (6-8 weeks old), CCT-Cre x P2X7fl/fl, LysM-Cre x P2X7fl/fl, CD4-Cre x P2X7fl/fl) model of LPS-induced ALI. To confirm the hypothesis we showed that intrapulmonary application of P2X7-antagonist KN62 prior (prophylactic) or 24 hours after (therapeutic) LPS instillation decreased neutrophil trafficking into the lungs, pro-inflammatory cytokines levels in bronchoalveolar fluid. <b>Conclusion:</b> Finally we can show that KN62 can reduce and prevent LPS induced lung inflammation. The experiments with P2X7-/- mice, chimera animals and celltype-specific P2X7-/- mice proved that the P2X7R on immune cells rather than lung tissue cells may play a central role in LPS-induced lung inflammation. This is a projection of a new therapeutically form, what can fully develop.

Highlights

  • According to the revised Berlin definition, the term acute respiratory distress syndrome (ARDS/acute lung injury (ALI)) describes an acutely developing and progressive hypoxic respiratory failure characterized by bilateral lung infiltrates on chest radiograph that cannot be explained by heart failure or a hypervolemic state [3,4,5]

  • Adenosine triphosphate (ATP) concentrations were markedly elevated in Bronchoalveolar lavage fluid (BALF) of patients with Acute respiratory distress syndrome (ARDS) compared with normal control subjects (Figure 1A)

  • To elucidate a possible role of Purinergic-type 2-receptor (P2R) signalling in the observed ATP and neutrophil accumulation in patients with ALI/ARDS we analysed ATP-Levels and cell counts in BALF in mice

Read more

Summary

Introduction

According to the revised Berlin definition, the term acute respiratory distress syndrome (ARDS/ALI) describes an acutely developing and progressive hypoxic respiratory failure characterized by bilateral lung infiltrates on chest radiograph that cannot be explained by heart failure or a hypervolemic state [3,4,5] This definition includes the formerly separate concept of acute lung injury (ALI) within the ARDS entity. Though novel therapeutic strategies including extracorporal membrane oxygenation have led to improved survival, the mortality of the most severe ARDS cases remains unacceptably high around 50–60% [6, 7]. Besides being characterized by more severe inflammation, shock and metabolic acidosis, this hyperinflammatory phenotype is associated with worse clinical outcome including a higher mortality despite usual therapeutic strategies [9]

Objectives
Methods
Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.