2004 IRISH SCIENTIST YEAR BOOK

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University College Dublin
Eavan Daly*
Neutrophil migration in the lung: an important target for therapies in inflammatory lung disease

The neutrophil is a white blood cell that defends the body when infection attacks. The neutrophil patrols the body with a 24-hour surveillance system, circulating in the blood stream and responding to alarm signals generated when infection strikes. When the neutrophil detects an alarm signal, it mobilises to move from the bloodstream to the site of infection, where it swallows the invading microorganisms and restores the normal environment. The neutrophil works in concert with other white blood cells in this manner to maintain healthy tissues throughout the body. This cycle of infection and resolution of infection is called inflammation. Inflammation is one of a host of effective defence mechanisms that ensures health and longevity.


A cartoon showing neutrophils migrating into tissue through endothelial cells lining a blood vessel. The neutrophils are depicted as purple cells and are migrating in response to an infectious signal seen here as blue dots.

The research conducted by our group centres on how the neutrophil responds to infection in one particular organ, the lung. The lung and the airways are quite susceptible to infection as many pathogens are airborne and the route of entry into the body is relatively unobstructed. When an otherwise healthy individual succumbs to an infection of the airways, the immune system mounts an inflammatory response resulting in the influx of neutrophils and other white blood cells to the lung airspace, and the infection is usually resolved in a matter of days without any complication. However, for a patient with an inflammatory lung disease, such as cystic fibrosis, emphysema, chronic obstructive pulmonary disorder or acute respiratory distress syndrome, the resolution of infection of the lung is much more difficult. While these disorders of the lung are a diverse collection of diseases with distinct causes and pathologies, the underlying immune response to infections is very similar. In most instances, there is a large and often excessive influx of neutrophils, and much damage to the lung tissue results from this sustained inflammatory response. One of the challenges in treating these diseases lies in attenuating the inappropriate influx of neutrophils without compromising the ability of the patient to fight normal infections.

In response to an infectious signal, messages are sent from protein to protein within the neutrophil in order to mobilise it to fight the infection. Part of this process involves activating particular proteins that will allow the neutrophil to move to the site of infection, where it can then swallow the invading microorganism. This process of relaying messages within the cell is called signal transduction. Another critical part of the neutrophil response to an infectious signal is to switch on the expression of certain genes to produce proteins that are essential for the resolution of infection.


Electron micrograph of a neutrophil migrating through an endothelial cell barrier

In our laboratory, we have developed an experimental system that models the blood to airspace barrier of the lung and enables us to study neutrophil migration across this barrier. This model provides invaluable insights into the genes and proteins that are involved in the process of migration. I am currently working to unravel some of the signalling pathways and gene expression profiles within the migrating neutrophil. I am carrying out this work in conjunction with several microscopy studies. This approach allows the visualisation of the neutrophils as they are migrating, and to correlate these images with the data that are obtained in the protein and gene assessment experiments.

Learning more about the messages that are relayed within the neutrophil as it migrates will result in a clear understanding of the proteins involved in the migratory pathways for many infectious signals. Armed with this information, targets for therapeutic intervention in inflammatory lung diseases can be identified. We then move a step closer to the lung-specific reduction of neutrophil migration in inflammatory lung disease.



* Eavan Daly was one of the winners in AccesScience '04 held in UCD in May 2004. Eavan works in Dr Clare O'Connor's Group. This is a summary of her presentation.

Contact: Eavan Daly, Department of Medicine and Therapeutics, Conway Institute, University College Dublin;
Tel: (01) 7166752; E-mail: [email protected] ; Web: http://www.ucd.ie/conway