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Updated: Feb 1, 2026
Basophil Activation Test for Investigation of IgE-Mediated Mechanisms in Drug Hypersensitivity
Published on: September 16, 2011
Basophils trigger emphysema development in a murine model of COPD through IL-4-mediated generation of
Sho Shibata1,2, Kensuke Miyake1, Tomoya Tateishi2
1Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Abstract:
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has generally been considered a non-Th2-type lung disorder, characterized by progressive airflow limitation with inflammation and emphysema, but its cellular and molecular mechanism remains ill defined, compared with that of asthma characterized by reversible airway obstruction. Here we show a previously unappreciated role for basophils at the initiation phase of emphysema formation in an elastase-induced murine model of COPD in that basophils represent less than 1% of lung-infiltrating cells. Intranasal elastase instillation elicited the recruitment of monocytes to the lung, followed by differentiation into interstitial macrophages (IMs) but rarely alveolar macrophages (AMs). Matrix metalloproteinase-12 (MMP-12) contributing to emphysema formation was highly expressed by IMs rather than AMs, in contrast to the prevailing assumption. Experiments using a series of genetically engineered mice suggested that basophil-derived IL-4, a Th2 cytokine, acted on lung-infiltrating monocytes to promote their differentiation into MMP-12-producing IMs that resulted in the destruction of alveolar walls and led to emphysema development. Indeed, mice deficient for IL-4 only in basophils failed to generate pathogenic MMP-12-producing IMs and hence develop emphysema. Thus, the basophil-derived IL-4/monocyte-derived IM/MMP-12 axis plays a crucial role in emphysema formation and therefore may be a potential target to slow down emphysema progression at the initiation phase of COPD.
Insights
Basophils initiate chronic obstructive pulmonary disease (COPD) emphysema by releasing IL-4, promoting monocyte differentiation into MMP-12-producing cells. Targeting this basophil-derived IL-4 pathway may slow emphysema progression.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Chronic obstructive pulmonary disease (COPD) is a major global health issue, often considered a non-Th2 lung disorder.
- The precise cellular and molecular mechanisms driving COPD, particularly emphysema, remain incompletely understood.
- Asthma, in contrast, is characterized by reversible airway obstruction and Th2-type inflammation.
Purpose of the Study:
- To investigate the role of basophils in the early stages of emphysema development in a murine model of COPD.
- To elucidate the cellular and molecular pathways involved in emphysema formation, focusing on immune cell interactions and cytokine signaling.
- To identify potential therapeutic targets for slowing emphysema progression.
Main Methods:
- Utilized an elastase-induced murine model of COPD.
- Analyzed lung-infiltrating cells, including monocytes, interstitial macrophages (IMs), and alveolar macrophages (AMs).
- Assessed the expression of Matrix metalloproteinase-12 (MMP-12) and the role of Interleukin-4 (IL-4) derived from basophils using genetically engineered mice.
Main Results:
- Basophils, though rare (<1%), were found to play a critical role in emphysema initiation.
- IL-4 secreted by basophils promoted the differentiation of monocytes into MMP-12-producing IMs.
- MMP-12 expression by IMs, not AMs, was crucial for alveolar wall destruction and emphysema development.
- Mice lacking basophil-derived IL-4 did not develop pathogenic IMs or emphysema.
Conclusions:
- A novel basophil-IL-4-monocyte-IM-MMP-12 axis is identified as critical for emphysema pathogenesis in COPD.
- Basophils are key initiators of emphysema, challenging the traditional view of COPD as a non-Th2 disease.
- This pathway represents a potential therapeutic target to mitigate emphysema progression in COPD patients.
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