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A Reversible, Non-invasive Method for Airway Resistance Measurements and Bronchoalveolar Lavage Fluid Sampling in Mice
Published on: April 13, 2010
Time-dependent analysis of bronchus-associated lymphoid tissue formation and pulmonary inflammation induced by
Wei Liu1, Akiko Honda1, Chihiro Morimoto1
1Department of Environmental Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501, Japan.
Abstract:
Particulate matter (PM) aggravates respiratory diseases, including asthma, and is associated with bronchus-associated lymphoid tissue (BALT) formation. However, the time-course effects of different PM types on pulmonary inflammation and BALT development remain unknown. Herein, we investigated the time-dependent effects of 3 PM types-titanium dioxide nanoparticles (TiO₂), diesel exhaust particles, and Asian sand dust-on lung inflammation and ectopic lymphoid tissue development over time, in the presence/absence of allergen ovalbumin. All PM types supported BALT formation, with stronger development when co-administered with ovalbumin. In allergen-treated mice, an early increase in interleukin-1α was followed by type 2 immune responses and BALT expansion. Under OVA-free conditions, despite the absence of an early interleukin-1α surge, adequate C-X-C motif chemokine ligand 1 production together with neutrophil accumulation was associated with BALT formation, particularly following repeated TiO₂ exposure. 3D lung reconstruction revealed that the progression of BALT and tertiary lymphoid structures extended from large airways to distal regions in the ovalbumin-treated groups exposed to TiO₂. TiO₂ was confirmed in the alveoli, alveolar macrophages, BALT areas, and hilar lymph nodes. These observations suggest that early elevation of interleukin-1α, adequate CXCL1 production, and neutrophil infiltration were associated with PM-induced BALT formation in a time- and context-dependent manner.
Insights
Different particulate matter (PM) types promote bronchus-associated lymphoid tissue (BALT) formation, especially with allergens. This occurs via distinct inflammatory pathways depending on PM type and exposure context.
Area of Science:
- Immunology
- Environmental Health
- Pulmonology
Background:
- Particulate matter (PM) exposure exacerbates respiratory conditions like asthma.
- PM is linked to bronchus-associated lymphoid tissue (BALT) formation in the lungs.
- The temporal dynamics of various PM types on lung inflammation and BALT remain unclear.
Purpose of the Study:
- To investigate the time-dependent effects of titanium dioxide nanoparticles (TiO₂), diesel exhaust particles, and Asian sand dust on pulmonary inflammation.
- To examine how these PM types influence BALT development over time, with and without ovalbumin (OVA) allergen exposure.
- To elucidate the underlying inflammatory mechanisms driving PM-induced BALT formation.
Main Methods:
- Comparative analysis of three PM types (TiO₂, diesel exhaust, Asian sand dust) in a mouse model.
- Assessment of lung inflammation and BALT formation at different time points.
- Evaluation of immune responses, including cytokine and chemokine production (e.g., IL-1α, CXCL1) and neutrophil infiltration.
- 3D lung reconstruction to visualize BALT and tertiary lymphoid structure progression.
- Localization studies of TiO₂ within lung tissues and lymph nodes.
Main Results:
- All tested PM types induced BALT formation, with enhanced development when co-administered with OVA.
- In OVA-treated mice, early IL-1α increase preceded type 2 immune responses and BALT expansion.
- In the absence of OVA, CXCL1 production and neutrophil infiltration were associated with BALT formation, particularly with repeated TiO₂ exposure.
- 3D reconstruction showed TiO₂-induced BALT and lymphoid structures extending from large airways to distal lung regions.
- TiO₂ particles were detected in alveoli, macrophages, BALT, and lymph nodes.
Conclusions:
- PM-induced BALT formation is time- and context-dependent.
- Early IL-1α elevation is crucial for BALT development in allergen-exposed settings.
- CXCL1 production and neutrophil infiltration play a significant role in BALT formation under non-allergic conditions, especially with TiO₂.
- These findings highlight the complex interplay between PM exposure, immune responses, and lung tissue remodeling.
