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Inflammation and leucocyte clearance from the lung

The pathogenesis of most respiratory diseases is associated with lung inflammation. A European project studied the mechanisms of leucocyte recruitment and how the subsequent clearing during resolution of inflammation was controlled.
Inflammation and leucocyte clearance from the lung
Leukocytes, or white blood cells, are recruited to the lung in the course of inflammatory respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis and pneumonia. Excessive leukocyte recruitment can lead to lung inflammation and it is essential that leukocytes are cleared efficiently once the infection has subsided.

The EU-funded project LUNG INFLAMMATION (An investigation into the differential mechanisms and regulation of leukocyte clearance from the human lung across two distinct barriers: the bronchial epithelium versus the alveolar epithelium) investigated the mechanisms involved in leucocyte trafficking across the alveolar and bronchial epithelia. Their particular objective was to study the involvement of the adhesion molecules in neutrophil trafficking.

Project researchers established a novel in vitro model of neutrophil trans-epithelial migration (TEpM) in normal human bronchial epithelial cells and human alveolar epithelial cells. The adhesion molecules of neutrophils involved in TEpM across the bronchial and alveolar epithelium were investigated using antibodies against candidate molecules.

The results demonstrated that migration of neutrophils across the bronchial epithelium required both CD11a/CD18 and CD11b/CD18 integrin adhesion molecules. At the same time, neutrophil TEpM across the alveolar epithelium was significantly inhibited only by blocking the expression of the CD11b/CD18 integrin molecule.

The project study was extended to examine the role of adhesion molecules in leukocytes recruitment to the lung using gene deficient mouse models and the mouse lipopolysaccharide model of inflammation.

Importantly, the LUNG INFLAMMATION study demonstrated a redundancy of the intercellular adhesion molecules ICAM-1 and ICAM-2 that were thought to play a key role in this process. The implications of this discovery are extensive and may explain why therapeutic targeting of these adhesion molecules has failed to translate into treatments for lung inflammation.

Related information


Inflammation, leucocyte clearance, lung, LUNG INFLAMMATION, adhesion molecule, integrin
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