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Researchers breathe new life into COPD research using mouse models
Researchers at Tokyo Medical and Dental University (TMDU) used mice to demonstrate that immune cells called basophils act to trigger a cascade of immune responses leading to airway degeneration resembling that in human chronic obstructive pulmonary disease (COPD).
In the study, published in the journal Proceedings of the National Academy of Sciences USA, researchers used a variety of mouse models to explain the developmental process behind COPD. The team showed that the immune cells basophils, previously believed to be mainly involved in fighting parasitic infections and inducing allergic responses, also induce the destruction of alveolar walls (emphysema).
“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,” the researchers noted.
Per reports on the study, the mice were first exposed to smoke, given the association between smoking and COPD, but there was no measurable “progressiveness of the disease in humans.” Next, researchers administered enzymes called proteases directly into the airway. Proteases break up proteins, producing more human COPD-like features.
They were able to induce emphysema in mice. Lead author, Sho Shibata, said the team then worked backwards one step at a time through the series of events causing this symptom to identify what started this cascade, using mice to knockout of each component of this cascade.
“The team started by revealing that the lung tissue destruction was caused by a molecule called MMP-12, which they found was released in excess from immune cells called interstitial macrophages when elastase was administered,” Science Daily reported.
By working backward, the researchers said they found “interstitial macrophages arose when the precursor immune cells called monocytes were induced by an immunity-regulating molecule called interleukin-4,” thus showing that this interleukin-4 was released by the immune cells basophils.
Ultimately, they were able to treat the mice that elicited emphysema.
"Our results are surprising because basophils have not previously been identified to be active in this kind of situation," said corresponding author Hajime Karasuyama. "It may be that basophils were previously overlooked because they only make up 1 percent of the white blood cells in the lungs."
The team hope that their discovery will lead to therapies targeting basophils or the interstitial macrophages that they create to slow down the progression of emphysema.
