GM-CSF-PPAR axis plays critical roles in the development, surfactant homeostasis and anti-inflammatory activity of alveolar macrophages

Abstract

AMΦs have an organ-specific function to maintain surfactant homeostasis that is critical to alveolar stability and lung function. AMΦs poses unique features such as aerobic respiration, high anti-oxidant capacity, and AMΦs alone among the all tissue MΦs are adapted to aerobic environment. Inflammation of the lungs causes respiratory failure and interferes with life sustaining. Therefore, treatment of foreign antigens with AMΦs should be done without inflammatory response as much as possible. AMΦs originate from fetal monocytes, are long-lived cells and their maintenance depend on self-renewing. GM-CSF is essential for the development of AMΦs but not other tissue MΦs. Characteristics of GM-CSF-induced human monocyte-derived MΦs (GM-MΦs) is the same as that of human AMΦs, indicating that the GM-MΦs become a model of human AMΦs. Expression of PPAR in nucleus of AMΦs depends on GM-CSF, and is essential for the development of AMΦs. Here, recent findings on the origin and the essential role of GM-CSF-PPAR axis in the development, surfactant homeostasis and anti-inflammatory activity of AMΦs are reviewed.