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Physiological function and potential therapeutic utility of the neuropeptide galanin in airway inflammation

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Neuropeptides — the contribution to asthma

Over the past few years there has been a dramatic increase in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease. European research has been finding therapeutic approaches using neuropeptides.

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Accumulating evidence points towards a strong connection between immune and neurogenic mechanisms in airway inflammation. This is further supported by the limited therapeutic efficacy of immune therapies. Asthma patients have higher levels of substance P, a neuropeptide that causes the pathology associated with inflamed airways. Another neuropeptide of widespread distribution, galanin is also encountered in the lung but it seems to counteract inflammation. Evidence so far indicates that it restricts blood flow and thus prevents immune cells from reaching the lungs and causing inflammation. Furthermore, mice deficient in galanin are unable to recruit neutrophils following an inflammatory stimulus. Based on these observations, researchers of the EU-funded AIRGAL project set out to investigate the function of galanin in the pulmonary system. They were particularly interested in the impact of galanin on neutrophil function. Neutrophils are actively involved in bronchial inflammation and tissue alterations through the release of myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) enzymes. During the AIRGAL study, it became evident that galanin works through the receptor GAL3 by modulation of neutrophil function and inducing white blood cell recruitment at inflamed vessels. Additionally, galanin might be implicated in the recruitment of alveolar macrophages, the first line of defence against inhaled substances and central to lung homoeostasis. Taken together, the delineation of the role of galanin in inflammation provides new therapeutic windows for inflammatory pulmonary diseases. Since alveolar macrophages are important for neonatal immunological responses, the outcome of the AIRGAL study may help to reduce their susceptibility to lung infection.

Keywords

Galanin, pulmonary inflammation, neutrophils, alveolar macrophages, enzymes, neuropeptide

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