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Pro-inflammatory effect of cystic fibrosis sputum microparticles in the murine lung
Chiara Porro1, Sante Di Gioia, Teresa Trotta
1Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Background:
The role of microparticles (MPs) in the inflammatory process of cystic fibrosis (CF) airways is not known. Here, we have studied the pro-inflammatory potential of CF MPs in a model of acute lung injury.
Methods:
Swiss mice were subjected to intratracheal administration of MPs obtained from CF and primary ciliary diskinesia (PCD) patients. Histopathology, total and differential cell counts in bronchoalveolar lavage fluid were used to evaluate the inflammatory reaction in the lung. Lipopolysaccharide (LPS)-like activity of MPs was studied by Limulus amebocyte lysate assay.
Results:
MPs obtained from acute CF patients determined peribronchial and perivascular inflammatory infiltrates similar to those elicited by LPS. This inflammation was granulocyte-dominated and higher than that determined by MPs obtained from stable CF, whereas PCD MPs caused a macrophage-dominated inflammation. While LPS-activity was not found in circulating blood MPs prepared from CF patients, it was present in MPs obtained from CF sputum and sputum CD66b(+) neutrophils. Finally, LPS-like activity was only detected in circulating MPs after incubation with LPS as well as in MPs obtained from LPS-stimulated neutrophils obtained from healthy donors.
Conclusions:
These data suggest that the pro-inflammatory potential of neutrophil-derived MPs in the CF airways may be subsequent to the binding of shedded LPS.
Insights
Microparticles (MPs) from cystic fibrosis (CF) patients induce lung inflammation. Neutrophil-derived MPs may contribute to CF airway inflammation by binding shed lipopolysaccharide (LPS).
Area of Science:
- Respiratory Medicine
- Immunology
- Cell Biology
Background:
- The role of microparticles (MPs) in cystic fibrosis (CF) airway inflammation remains unclear.
- This study investigates the pro-inflammatory potential of CF MPs in an acute lung injury model.
Purpose of the Study:
- To assess the inflammatory effects of MPs from CF patients compared to primary ciliary diskinesia (PCD) patients.
- To investigate the lipopolysaccharide (LPS)-like activity of these MPs.
Main Methods:
- Intratracheal administration of MPs from CF and PCD patients into mice.
- Evaluation of lung inflammation via histopathology and bronchoalveolar lavage fluid analysis.
- Limulus amebocyte lysate assay to detect LPS-like activity in MPs.
Main Results:
- MPs from acute CF patients induced significant peribronchial and perivascular inflammation, similar to LPS.
- Inflammation induced by CF MPs was granulocyte-dominated and more pronounced than from stable CF patients.
- PCD MPs induced macrophage-dominated inflammation; LPS-like activity was found in CF sputum MPs and stimulated neutrophils, not circulating CF MPs.
Conclusions:
- Neutrophil-derived MPs in CF airways may exert pro-inflammatory effects through binding shed LPS.
- This mechanism highlights a potential pathway for inflammation in CF lung disease.
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