Discussion

Alveolar macrophages exist in a unique microenvironment and, despite historical evidence showing that they are in close contact with the respiratory epithelium, have until recently been investigated in isolation. The microenvironment of the airway lumen has a considerable influence on many aspects of alveolar macrophage phenotype, function and turnover. As the lungs adapt to environmental challenges, so too do alveolar macrophages adapt to accommodate the ever-changing needs of the tissue. I will discuss how working in an open innovation, pre-competitive environment with the UK’s largest pharmaceutical companies allows us to explore the unique characteristics of alveolar macrophages, the mechanisms that drive their adaptation and the direct and indirect influences of epithelial cells on them. I will also highlight how they adapt in the inflamed lung and the processes driving adaptation in a variety of inflammatory conditions. The unique tissue location and function of alveolar macrophages distinguish them from other macrophage populations. However, over-regulation of them in repair leads to bacterial exacerbations. Re-setting the inflammatory tone of the airspaces and particularly airway macrophages presents new therapeutic opportunities.