Review articleInterplay of extracellular matrix and leukocytes in lung inflammation

- Leukocytes interact with lung extracellular matrix (ECM) during inflammation.
- This interaction affects how leukocytes accumulate, migrate, and differentiate.
- Versican and hyaluronan are ECM components that regulate leukocyte phenotype.
- Versican and hyaluronan increase in a range of lung diseases.
- Macrophages can both promote and resolve inflammation and are influenced by MMP10.

During inflammation, leukocytes influx into lung compartments and interact with extracellular matrix (ECM). Two ECM components, versican and hyaluronan, increase in a range of lung diseases. The interaction of leukocytes with these ECM components controls leukocyte retention and accumulation, proliferation, migration, differentiation, and activation as part of the inflammatory phase of lung disease. In addition, bronchial epithelial cells from asthmatic children co-cultured with human lung fibroblasts generate an ECM that is adherent for monocytes/macrophages. Macrophages are present in both early and late lung inflammation. Matrix metalloproteinase 10 (MMP10) is induced in alveolar macrophages with injury and infection and modulates macrophage phenotype and their ability to degrade collagenous ECM components. Collectively, studies outlined in this review highlight the importance of specific ECM components in the regulation of inflammatory events in lung disease. The widespread involvement of these ECM components in the pathogenesis of lung inflammation make them attractive candidates for therapeutic intervention.