GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis.
N Engl J Med
; 356(6): 567-79, 2007 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-17287477
ABSTRACT
BACKGROUND:
Increased mortality from infection in patients with pulmonary alveolar proteinosis occurs in association with high levels of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We tested the hypothesis that neutrophil functions are impaired in patients with pulmonary alveolar proteinosis and that GM-CSF autoantibodies cause the dysfunction.METHODS:
We studied 12 subjects with pulmonary alveolar proteinosis, 61 healthy control subjects, and 12 control subjects with either cystic fibrosis or end-stage liver disease. We also studied GM-CSF-/- mice and wild-type mice. We evaluated basal neutrophil functions, neutrophil functions after priming by GM-CSF to augment antimicrobial functions, and the effects of highly purified GM-CSF autoantibodies on neutrophil functions in vitro and in vivo.RESULTS:
Neutrophils from subjects with pulmonary alveolar proteinosis had normal ultrastructure and differentiation markers but impaired basal functions and antimicrobial functions after GM-CSF priming. GM-CSF-/- mice also had reduced basal neutrophil functions, but functions after GM-CSF priming were unimpaired. The neutrophil dysfunction characteristic of pulmonary alveolar proteinosis was reproduced in a dose-dependent fashion in blood specimens from healthy control subjects after incubation with affinity-purified GM-CSF autoantibodies isolated from patients with pulmonary alveolar proteinosis. The injection of mouse GM-CSF antibodies into wild-type mice also caused neutrophil dysfunction.CONCLUSIONS:
The antimicrobial functions of neutrophils are impaired in patients with pulmonary alveolar proteinosis, owing to the presence of GM-CSF autoantibodies. The effects of these autoantibodies show that GM-CSF is an essential regulator of neutrophil functions.
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Base de dados:
MEDLINE
Assunto principal:
Proteinose Alveolar Pulmonar
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Autoanticorpos
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Fator Estimulador de Colônias de Granulócitos e Macrófagos
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Neutrófilos
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Animals
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article