GM-CSF Autoantibodies and Neutrophil Dysfunction in Pulmonary Alveolar Proteinosis

Infection, especially with opportunistic microbes, is a prominent feature of pulmonary alveolar proteinosis; extrapulmonary infection suggests a systemic susceptibility. The authors show that neutrophil functions (phagocytosis, adhesion, oxidative burst, and bactericidal activity) are depressed in p...

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Bibliographic Details
Published in:	The New England journal of medicine Vol. 356; no. 6; pp. 567 - 579
Main Authors:	Uchida, Kanji, Beck, David C, Yamamoto, Takashi, Berclaz, Pierre-Yves, Abe, Shuichi, Staudt, Margaret K, Carey, Brenna C, Filippi, Marie-Dominique, Wert, Susan E, Denson, Lee A, Puchalski, Jonathan T, Hauck, Diane M, Trapnell, Bruce C
Format:	Journal Article
Language:	English
Published:	Boston, MA Massachusetts Medical Society 08-02-2007
Subjects:	Adolescent Adult Aged Animals Apoptosis Autoantibodies - physiology Biological and medical sciences Case-Control Studies Child Cystic Fibrosis - immunology Female Flow cytometry General aspects Granulocyte-Macrophage Colony-Stimulating Factor - immunology Granulocyte-Macrophage Colony-Stimulating Factor - physiology Humans Infections Leukocyte Count Liver Diseases - immunology Lungs Male Medical sciences Mice Mice, Inbred Strains Middle Aged Mortality Neutrophils - physiology Neutrophils - ultrastructure Pulmonary Alveolar Proteinosis - immunology Surfactants Autoimmunity Medicine Lung disease Pulmonary alveolar proteinosis Respiratory disease Antibody Dysfunction Granulocyte Autoantibody Neutrophil Granulocyte macrophage colony stimulating factor
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Summary:	Infection, especially with opportunistic microbes, is a prominent feature of pulmonary alveolar proteinosis; extrapulmonary infection suggests a systemic susceptibility. The authors show that neutrophil functions (phagocytosis, adhesion, oxidative burst, and bactericidal activity) are depressed in patients with pulmonary alveolar proteinosis and that the cause is autoantibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF). These findings clearly demonstrate the essential role of GM-CSF in the antimicrobial activities of neutrophils. The authors show that neutrophil functions are depressed in patients with pulmonary alveolar proteinosis and that the cause is autoantibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF). Pulmonary alveolar proteinosis 1 is a rare disorder in which surfactant accumulates within pulmonary alveoli, causing respiratory insufficiency. 2 , 3 The disease is specifically associated with high levels of autoantibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF) in blood and tissues, including pulmonary alveoli. 4 These autoantibodies neutralize the biologic activity of GM-CSF. 5 In mice, GM-CSF stimulates the terminal differentiation of alveolar macrophages, primarily through the action of the transcription factor PU.1. 6 The homozygous deletion of GM-CSF genes causes pulmonary alveolar proteinosis in mice 7 , 8 by impairing the clearance of pulmonary surfactant by alveolar macrophages that are dependent on GM-CSF. 9 In patients with pulmonary alveolar . . .
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0028-4793 1533-4406
DOI:	10.1056/NEJMoa062505