Clinical immunology : the official journal of the Clinical Immunology Society
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Granulocyte-macrophage colony stimulating factor (GM-CSF) deficient mice develop a pulmonary alveolar proteinosis (PAP) syndrome which is corrected by the administration/expression of GM-CSF. These observations implicate GM-CSF in the pathogenesis of human PAP. We hypothesized that human PAP may involve an intrinsic cellular defect in monocytes/macrophages with an inability to produce GM-CSF and/or respond to GM-CSF. ⋯ IL-10 is a potent inhibitor of LPS-stimulated GM-CSF production from healthy control alveolar macrophages. These studies are the first to demonstrate that circulating monocytes and alveolar macrophages from PAP patients are able to synthesize GM-CSF and respond to GM-CSF, suggesting no intrinsic abnormalities in GM-CSF signaling. In addition, these observations suggest that PAP in a subset of patients is the result of decreased availability of GM-CSF due to GM-CSF blocking activity and reduced GM-CSF production by IL-10.