| Pulmonary alveolar proteinosis: a bench-to-bedside story of granulocyte-macrophage colony-stimulating factor dysfunction. | |
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MedLine Citation:
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PMID: 19666756 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by ineffective clearance of surfactant by alveolar macrophages. Through recent studies with genetically altered mice, the etiology of this idiopathic disease is becoming clearer. Functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) appears to contribute to disease pathogenesis because mutant mice deficient in GM-CSF or its receptor spontaneously develop PAP. Recent human studies further suggest a connection between PAP and defective GM-CSF activity because inactivating anti-GM-CSF autoantibodies are observed in all patients with idiopathic PAP, and additional rare cases of PAP in children have been accompanied by genetic defects in the alpha chain of the GM-CSF receptor. In patients and mouse models of PAP, deficient GM-CSF activity appears to result in defective alveolar macrophages that are unable to maintain pulmonary surfactant homeostasis and display defective phagocytic and antigen-presenting capabilities. The most recent studies also suggest that neutrophil dysfunction additionally contributes to the increased susceptibility to lung infections seen in PAP. Because the phenotypic and immunologic abnormalities of PAP in mouse models can be corrected by GM-CSF reconstituting therapies, early clinical trials are underway utilizing administration of GM-CSF to potentially treat human PAP. The development of novel treatment approaches for PAP represents a dramatic illustration in pulmonary medicine of the "bench-to-bedside" process, in which basic scientists, translational researchers, and clinicians have joined together to rapidly take advantage of the unexpected observations frequently made in the modern molecular biology research laboratory. |
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Authors:
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Sara R Greenhill; Darrell N Kotton |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Chest Volume: 136 ISSN: 1931-3543 ISO Abbreviation: Chest Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-11 Completed Date: 2009-09-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0231335 Medline TA: Chest Country: United States |
Other Details:
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Languages: eng Pagination: 571-7 Citation Subset: AIM; IM |
Affiliation:
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Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bronchoalveolar Lavage Fluid / cytology Cohort Studies Disease Models, Animal Follow-Up Studies Granulocyte Macrophage Colony-Stimulating Factors, Recombinant / therapeutic use* Granulocyte-Macrophage Colony-Stimulating Factor / deficiency* Humans Lung / pathology* Mice Mice, Knockout Pulmonary Alveolar Proteinosis / diagnosis*, genetics, physiopathology Risk Assessment Survival Analysis Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Granulocyte Macrophage Colony-Stimulating Factors, Recombinant; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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