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lüll Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages Trapnell BC; Carey BC; Uchida K; Suzuki TCurr Opin Immunol 2009[Oct]; 21 (5): 514-21Pulmonary 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.|Animals[MESH]|Cell Differentiation/immunology[MESH]|Granulocyte-Macrophage Colony-Stimulating Factor/*immunology/metabolism[MESH]|Humans[MESH]|Lung/immunology/metabolism/pathology[MESH]|Macrophages, Alveolar/*immunology/metabolism/pathology[MESH]|Models, Biological[MESH]|Protein Binding[MESH]|Pulmonary Alveolar Proteinosis/*immunology/metabolism[MESH]|Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/*immunology/metabolism[MESH] |