Journal Article

GM-CSF Autoantibodies and Neutrophil Dysfunction in Pulmonary Alveolar Proteinosis

Filippi, Marie-Dominique, Berclaz, Pierre-Yves, Hauck, Diane M, Abe, Shuichi, Denson, Lee A, Wert, Susan E, Puchalski, Jonathan T, Trapnell, Bruce C, Carey, Brenna C, Uchida, Kanji, Staudt, Margaret K, Yamamoto, Takashi, Beck, David C

2007

Overview

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 . . .

• Publisher: Massachusetts Medical Society
• Subject: 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