Airways and Lungs

The airways and lungs are affected by a range of diseases, but while some have been well characterized and treated, others such as chronic obstructive pulmonary disorder (COPD) are still somewhat of an enigma. This condition is known to involve a variety of progressively deteriorating symptoms such as inflammation of the lungs and narrowing of the airways, but the causes of these at the cellular and molecular levels have largely obscure.
In a landmark study recently published in the journal Proceedings of the National Academy of Sciences USA; a research team from Tokyo Medical and Dental University (TMDU) have used a variety of models to explain the developmental process behind COPD. The team showed that the immune cells basophils; previously believed to 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. First,  to smoke; given the association between smoking and COPD; but this failed to mirror the progressiveness of the disease in humans even after they quit smoking. This by the approach of administering enzymes called proteases directly into the airway. Proteases break up proteins; producing more human COPD-like features.
“Here, they induced emphysema; using a protease called elastase,” lead author Sho Shibata says, “then worked backward one step at a time through the series of cellular and molecular events causing this symptom to identify what started this cascade; using mice with knockout of each component of this cascade.”

Lung Tissue Destruction

The team revealing that the lung tissue destruction is caused by a molecule called MMP-12; which they found released in excess from immune cells called interstitial macrophages when elastase administered. They then that these interstitial macrophages arose when the precursor immune cells monocytes are inducing by an immunity-regulating molecule interleukin-4. Looking backward another step in this chain; the team showing that this interleukin-4 release by the immune cells basophils.

Control (left panel) or basophil-deplete  (right panel) were intranasally treating once with porcine pancreatic elastase to elicit emphysema. “the results are surprising because basophils have not previously identifies to  active in this kind of situation;” corresponding author Hajime Karasuyama says. “It may that basophils are  overlook because they only make up 1% of the white blood cells in the lungs.”

Basophil-derived IL-4/monocyte-derived IM/MMP-12 axis plays a crucial role in emphysema formation. The team hopes that their discovery will lead to therapies targeting basophils or the interstitial macrophages that they create to slow down the progression of emphysema.