Is There More to Lung Development Than Steroids and Surfactant?

There has been a recent renaissance in the field of lung development. More has been learned about how the lungs are formed and how they grow in the last 10 years than in all the prior years combined. Striking parallels have emerged between mouse models and actual human diseases and developmental defects. The following is a brief review of our current understanding of the regulating factors and their interactions.

One of the most interesting of the recent insights into pulmonary molecular physiology occurred by pure serendipity. Pulmonary alveolar proteinosis (PAP) is an extraordinary disease in which the lungs are filled with a proteinaceous, lipid-rich material. Little was known about the cause. Then oncologist Glenn Dranoff and colleagues,¹ attempting to identify molecules that could be useful in enhancing tumor vaccines, created a knockout mouse of granulocyte-macrophage colony-stimulating factor (GM-CSF). Surprisingly, the mice had no abnormalities of immunity, but they were born with lungs that resembled those of human patients with PAP. Indeed, it appears that GM-CSF regulates the clearance of surfactant from the lung by macrophages. Some patients with PAP actually have a defect in the GM-CSF receptor. Fortunately, these …

Address correspondence to T. Bernard Kinane, MD, Pediatric Pulmonary Unit, Vincent Burham Basement, 55 Fruit St, Massachusetts General Hospital, Boston, MA 02114. E-mail:kinane{at}helix.mgh.harvard.edu