Dr Madsen’s research area is mainly focused on the role of innate immune proteins in health and disease. He is particular focusing on a group of proteins called ‘collectins’, which are a part of the innate immune system, but also have additional roles in the adaptive immune system.

 

Collectins are oligomerised C-type lectins (sugar-binding proteins) with a collagenous domain, hence the name col-lectin. They bind to certain carbohydrates found on the surface of viruses, bacteria and other glycosylated micro particles like pollen. Collectins facilitate clearance of these particles from the body using clearance mechanisms such as the mucocillial staircase in the airways and phagocytosis by immune cells such as macrophages, dendritic cells and neutrophils.

 

Dr Madsen has a particular interest in the collectins Surfactant Protein A (SP-A) and Surfactant Protein D (SP-D). These proteins were originally identified in surfactant, the lining fluid of the lungs responsible for lowering surface tension in the lungs of mammals. SP-D is not only present in the lung but also expressed in epithelial cells throughout the body, located on all mucosal surfaces and secreted to and found in several body fluids such as saliva and tears. At these sites, SP-D facilitates clearance of potential pathogenic microorganisms like viruses and bacteria, but the protein is also involved in the normal homeostasis of apoptotic and necrotic cells, hence both SP-A and SP-D are key components involved in recognition and clearance of altered and non-self-targets.

 

Dr Madsen is investigating, in collaboration with Prof Howard Clark, Professor of Neonatal Medicine and Child Health, the roles of SP-A and SP-D in health and disease. The collaborative research also focuses currently on whether recombinant fragment of human innate immunity proteins, such as SP-D, can be used as a potential therapeutic against respiratory diseases and in addition treatment of inflammatory conditions such as asthma, cystic fibrosis, neonatal chronic lung disease and adult emphysema.

 

Recently, a new research interest in nanoparticles has been pursued. Nanoparticles are very small (have at least one dimension in the nanometre scale) and due to their small size can enter the lower airways where the gas exchange take place. The airways are indeed the primary route of nanoparticle exposure in humans and the increased usage in modern life products has raised concern about the safe usage of these. Nanoparticles have a size similar to many viruses and in the aggregated state a size similar to bacteria. We have shown that both SP-A and SP-D binds to the nanoparticles and can modify the behaviour of these particles, which could have big impact in vivo in exposed individuals. Furthermore, if the nanoparticles bind all the available SP-A and SP-D in the lungs, which would make individuals deficient in these proteins and thereby affected individuals could become more susceptible to virus and bacterial infections. This could have a big impact in people with chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), which already have a reduced lung capacity.