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Immune Dysregulation in the Pathogenesis of Pulmonary Alveolar Proteinosis

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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 α 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.

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Acknowledgment

This work was supported in part by grants from the National Institutes of Health (AI063178 to Dr. Martinez-Moczygemba; U19AI071130 and AI36936 to Dr. Huston).

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. 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, Suite 803, Houston, TX, 77030, USA

    Margarita Martinez-Moczygemba & David P. Huston

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  1. Margarita Martinez-Moczygemba
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  2. David P. Huston
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Correspondence to David P. Huston.

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Martinez-Moczygemba, M., Huston, D.P. Immune Dysregulation in the Pathogenesis of Pulmonary Alveolar Proteinosis. Curr Allergy Asthma Rep 10, 320–325 (2010). https://doi.org/10.1007/s11882-010-0134-y

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