AsianScientist (Feb. 11, 2019) – Scientists in Japan have discovered that a subtype of immune cells known as basophils are involved in the development of chronic obstructive pulmonary disorder (COPD). They published their findings in the Proceedings of the National Academy of Sciences.
The World Health Organization estimates that some 65 million people around the world suffer from COPD, which is known to involve a variety of progressively deteriorating symptoms such as inflammation of the lungs and narrowing of the airways. However, the causes of these symptoms at the cellular and molecular levels have largely remained obscure.
In the present study, researchers led by Professor Sho Shibata of Tokyo Medical and Dental University (TMDU) have shown that immune cells called basophils act to trigger a cascade of immune responses leading to airway degeneration resembling that in human COPD.
Earlier studies of COPD focused on mice as a suitable model for easily dissecting the mechanisms behind this disease, but encountered a range of difficulties in mimicking the features in humans. For example, mice were exposed to smoke, but the approach failed to mirror the progression of the disease in humans after smoking cessation.
“Here, we induced emphysema (destruction of the lung air sacs) in model mice using a protease called elastase,” said Sho. “We then worked backwards one step at a time through the series of cellular and molecular events causing this symptom [in genetically modified mice].”
The team revealed that elastase resulted in the excessive release of a molecule called MMP-12 by interstitial macrophages, a type of immune cell in the lungs. MMP-12 was responsible for lung tissue destruction.
The researchers next identified the source of the interstitial macrophages. They discovered that basophils—previously believed to be mainly involved in fighting parasitic infections and inducing allergic responses—released an immunity-regulating molecule called interleukin-4 to cause the accumulation of interstitial macrophages in the lungs.
“Our results are surprising because basophils have not previously been identified to be active in this kind of situation,” said corresponding author Professor Hajime Karasuyama of TMDU. “It may be that basophils were previously overlooked because they only make up one percent of the white blood cells in the lungs.”
The team hope that their discovery will lead to therapies targeting basophils or interstitial macrophages to slow down the progression of emphysema.
The article can be found at: Shibata et al. (2018) Basophils Trigger Emphysema Development in a Murine Model of COPD Through Il-4–mediated Generation of MMP-12–producing Macrophages.
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Source: Tokyo Medical and Dental University; Photo: Shutterstock.
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