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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Pulmonary alveolar proteinosis is a disease of decreased availability of GM-CSF rather than an intrinsic cellular defect.
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Pulmonary alveolar proteinosis is a disease of decreased availability of GM-CSF rather than an intrinsic cellular defect.

机译：肺泡蛋白沉着症是一种GM-CSF可用性降低的疾病，而不是内在的细胞缺陷。

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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. Thus, we investigated the cytokine responses to GM-CSF and LPS from peripheral blood monocytes and alveolar macrophages from patients with idiopathic PAP and healthy controls. Macrophage inflammatory protein-1-alpha (MIP) was measured from GM-CSF-stimulated cells and GM-CSF was measured from LPS-stimulated cells by ELISA. The MIP and GM-CSF production by monocytes and alveolar macrophages did not differ between PAP patients and healthy controls. Growth of the GM-CSF-dependent human myeloid cell line TF-1 was inhibited by serum from all patients studied (n = 10) and all patients had anti-GM-CSF antibody in their serum. The BAL from PAP patients had less detectable GM-CSF by ELISA than healthy controls (P = 0.05); in contrast, the inhibitory cytokine, interleukin-10 (IL-10), was increased in PAP compared to controls (P = 0.04). 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. Copyright 2000 Academic Press.
机译：粒细胞-巨噬细胞集落刺激因子（GM-CSF）缺陷的小鼠发展成肺泡蛋白沉着症（PAP）综合征，可通过施用/表达GM-CSF来纠正。这些观察暗示GM-CSF在人类PAP的发病机理中。我们假设人类PAP可能涉及单核细胞/巨噬细胞中的固有细胞缺陷，无法产生GM-CSF和/或对GM-CSF反应。因此，我们调查了特发性PAP患者和健康对照者对外周血单核细胞和肺泡巨噬细胞对GM-CSF和LPS的细胞因子反应。通过ELISA从GM-CSF刺激的细胞中测量巨噬细胞炎性蛋白-1-α（MIP），从LPS刺激的细胞中测量GM-CSF。在PAP患者和健康对照之间，单核细胞和肺泡巨噬细胞产生的MIP和GM-CSF没有差异。所有研究的患者（n = 10）的血清均抑制了GM-CSF依赖性人骨髓细胞TF-1的生长，所有患者的血清中均含有抗GM-CSF抗体。 PAP患者的BAL经ELISA检测的GM-CSF较健康对照组少（P = 0.05）;相反，PAP中的抑制性细胞因子白细胞介素10（IL-10）与对照组相比有所增加（P = 0.04）。 IL-10是有效抑制LPS刺激的健康对照肺泡巨噬细胞产生GM-CSF的抑制剂。这些研究首次证明来自PAP患者的循环单核细胞和肺泡巨噬细胞能够合成GM-CSF并对GM-CSF做出反应，提示GM-CSF信号传导没有内在异常。此外，这些观察结果表明，一部分患者中的PAP是GM-CSF阻断活性导致GM-CSF可用性降低以及IL-10导致GM-CSF产量降低的结果。版权所有2000学术出版社。

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