Figure 7.

Schematic representation of the key findings of the present study In healthy lungs, alveolar macrophages survey the alveoli and remove pathogens and debris to enable proper gas exchange. In the alveoli of COPD patients, the alveolar macrophages accumulate cholesteryl esters. In addition, blood monocytes invade the alveoli and differentiate into alveolar macrophages. The transcriptome of COPD alveolar macrophages indicate TGF-β1-associated cell signaling especially in the early stages of monocyte-to-macrophage differentiation. The alveolar macrophages in COPD show a reduced ability to migrate towards chemokine. Furthermore, they express fewer MHC molecules; especially MHC class I. Together with the reduced phagocytosis of alveolar macrophages in COPD, the ability of these cells for immune surveillance is severely limited during the disease. In addition, their mitochondria are leaking (e.g. to protons) and therefore produce high amounts of reactive oxygen species. Taken together, the guardians of normal lung function (alveolar macrophages) are severely altered in COPD, preventing them from fulfilling their important physiological functions properly. Furthermore, the observation of reduced MHC expression in blood monocytes indicates that the manifestation of COPD has a strong systemic component.