Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages.
Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of pulmonary surfactant, respiratory insufficiency, and increased infections. It occurs in various clinical settings that disrupt surfactant catabolism in alveolar macrophages, including a relatively more common autoimmune disease caused by GM-CSF autoantibodies and a rare congenital disease caused by CSF2RA mutations. Recent results demonstrate that GM-CSF is crucial for alveolar macrophage terminal differentiation and immune functions, pulmonary surfactant homeostasis, and lung host defense. GM-CSF is also required to determine the basal functional capacity of circulating neutrophils, including adhesion, phagocytosis, and microbial killing. PAP research has illuminated the crucial role of GM-CSF in innate immunity and led to novel therapy for PAP and the potential use of anti-GM-CSF therapy in other common disorders.
Trapnell
Bruce C
BC
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Bruce.Trapnell@cchmc.org
Carey
Brenna C
BC
Uchida
Kanji
K
Suzuki
Takuji
T
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D011485:Protein Binding; D011649:Pulmonary Alveolar Proteinosis / Q000276:immunology* / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism
C521678:CSF2RA protein, human; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor