Marie Curie Actions: Inspiring Researchers - Imdea

Breakingthe strangleholdof asthmaSmooth muscle is the tissue that lines all hollow organsand vessels in the human body, including the airways in therespiratory tract. In many diseases of the airways, such asasthma, chronic obstructive pulmonary disease (COPD), cysticfi brosis and bronchopulmonary dysplasia, the airway smoothmuscle behaves aberrantly. ‘In these diseases, particularlyin asthma, there is an increase in airway smooth musclemass and an increased capacity of the muscle to constrictthe airways,’ explains Dr Gosens. While the reason for thisis not yet fully understood, ‘pathological changes in airwaysmooth muscle behaviour are considered a primary causeof exaggerated airway narrowing in asthmatics, resulting inchest tightness’.Little folds, big impactIn his Caveolins project, Dr Gosens analysed how caveolae, thespecial signalling hot spots in the cell membrane, contributeto the abnormal response of smooth muscle in asthma. ‘Inthese caveolae, little folds or invaginations in the small plasmamembrane that are abundant in smooth muscle cells, manysignalling proteins and receptors are clustered,’ he says. Theseproteins and receptors, in turn, regulate the cells’ response totheir environment and initiate cell growth, cell contraction or thesecretion of enzymes, for instance. ‘These processes are notfunctioning properly in asthma, in which the muscle constricts tooeasily and too much in response to the infl amed environment,’Dr Gosens describes.This is an observation which he decided to put to good use.Understanding the goings-on in the caveolae, he speculated,should help to understand the irregularities in the airway smoothmuscle growth and reaction, and so offer scope to fi nd newtreatment methods for asthma. And the Dutchman’s researchwith renowned expert Dr Andrew J. Halayko at the ManitobaInstitute of Child Health in Canada produced the results hehad hoped for.Contractile airway smooth muscle cells in culture© Dr Reinoud Gosens/Dr Andrew J. Halayko269