Related Experiment Videos
Anti-inflammatory responses and oxidative stress in Nippostrongylus brasiliensis-induced pulmonary inflammation
Kathryn S McNeil1, David P Knox, Lorna Proudfoot
1School of Life Sciences, Napier University, Edinburgh, UK.
Abstract:
Migration of L3 larvae of Nippostrongylus brasiliensis through the lungs of the rat, during primary infection, was studied at 24 h, 72 h and 8 days. At 24 h p.i., there was evidence of damage to lung epithelial cells and microvasculature, with increased protein and gamma-glutamyl transpeptidase in the bronchoalveolar lavage (BAL) fluid. However, there was little evidence of inflammatory cell recruitment. At 24 h p.i., there was a significant reduction in the inflammatory cytokine tumour necrosis factor alpha. Superoxide (O2-*) production was also reduced, accompanied by an increase in superoxide dismutase activity. Lipid peroxidation was reduced at 24 h p.i. and L3 larvae were shown to possess high levels of glutathione compared to host lung tissue. Nitric oxide, detected as nitrite, was produced in BAL fluid, and inducible nitric oxide synthase protein was increased by 72 h p.i. There was evidence of peroxynitrite production throughout the infection period with specific protein bands nitrosylated at 75, 30 and 25 kDa. It appears that despite early evidence of lung damage, the inflammation was reduced in response to L3 larvae of N. brasiliensis.
Insights
Nippostrongylus brasiliensis larvae cause early lung damage but reduce inflammation. Despite initial injury, the host response shows decreased inflammatory cytokines and oxidative stress markers.
Area of Science:
- Immunology
- Parasitology
- Pulmonology
Background:
- Nippostrongylus brasiliensis (N. brasiliensis) is a nematode parasite that infects rodents.
- Lung migration is a critical stage in the N. brasiliensis life cycle, involving host-parasite interactions within lung tissue.
Purpose of the Study:
- To investigate the host immune response and tissue damage during the lung migration of L3 larvae of N. brasiliensis in rats.
- To characterize early inflammatory and oxidative stress markers in bronchoalveolar lavage (BAL) fluid.
Main Methods:
- Analysis of bronchoalveolar lavage (BAL) fluid at 24 hours, 72 hours, and 8 days post-infection (p.i.).
- Measurement of protein, gamma-glutamyl transpeptidase, inflammatory cytokines (tumor necrosis factor alpha), oxidative stress markers (superoxide, lipid peroxidation), and nitric oxide metabolites.
- Assessment of antioxidant enzyme activity (superoxide dismutase) and protein nitrosylation.
Main Results:
- Early lung damage observed at 24 h p.i. with increased protein and gamma-glutamyl transpeptidase in BAL fluid.
- Paradoxically, reduced inflammatory cell recruitment and decreased tumor necrosis factor alpha at 24 h p.i.
- Modulation of oxidative stress with reduced superoxide production and lipid peroxidation, alongside increased superoxide dismutase activity.
- Evidence of nitric oxide production and peroxynitrite formation throughout the infection.
Conclusions:
- Despite initial lung epithelial and microvascular damage, N. brasiliensis L3 larvae appear to suppress the inflammatory response.
- The parasite may employ mechanisms involving antioxidant systems and nitric oxide to modulate host inflammation during lung migration.