title: Immune dysregulation in the pathogenesis of pulmonary alveolar proteinosis.
abstract: Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the alpha chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense.
authors.affiliation: Departments of Microbial and Molecular Pathogenesis and Medicine, College of Medicine and Clinical Science and Translational Research Institute, Texas A&M Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030, USA. mmoczygemba@medicine.tamhsc.edu
authors.forename: Margarita
authors.initials: M
authors.lastname: Martinez-Moczygemba
authors.forename: David P
authors.initials: DP
authors.lastname: Huston
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D000918:Antibody Specificity; D015551:Autoimmunity / Q000276:immunology; D002452:Cell Count; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D009154:Mutation; D011649:Pulmonary Alveolar Proteinosis / Q000276:immunology* / Q000503:physiopathology* / Q000628:therapy; D011650:Pulmonary Alveoli / Q000503:physiopathology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D057134:Antibodies, Neutralizing; C521678:CSF2RA protein, human; D008074:Lipoproteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor