Attenuated hematopoietic response to granulocyte-macrophage colony- stimulating factor in patients with acquired pulmonary alveolar proteinosis

Abstract

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing β-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 μg/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor α- and β-common ch..