Effect of bronchoalveolar lavage fluid from Pneumocystis carinii-infected hosts on phagocytic activity of alveolar macrophages
Effect of bronchoalveolar lavage fluid from Pneumocystis carinii-infected hosts on phagocytic activity of alveolar macrophages
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DOI：
10.1128/iai.72.4.2140-2147.2004
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发表时间：
2004-04-01
影响因子：
3.1
通讯作者：
Lee, CH
中科院分区：
文献类型：
--
作者：
Lasbury, ME;Lin, P;Lee, CH
卡氏肺孢子虫感染大鼠肺泡巨噬细胞吞噬功能缺陷。为了研究这种缺陷是否是由于卡氏肺孢子虫感染的肺中存在的某种因子，将未感染大鼠的肺泡巨噬细胞与卡氏肺孢子虫感染大鼠的支气管肺泡灌洗液（BAL）样品一起孵育。肺泡巨噬细胞与这些BAL液样本治疗变得有缺陷的吞噬功能，但保持正常时，与BAL液样本从未感染或弓形虫感染的大鼠。当使来自卡氏肺孢子虫感染大鼠的BAL液样品通过孔径为0.45 μ m的过滤器时，保留了BAL液样品对吞噬作用的抑制活性，但当用蛋白酶如胰蛋白酶、胃蛋白酶、木瓜蛋白酶或内肽酶Gly-C消化BAL液样品时，抑制活性丧失。这些BAL液样品的脂质组分对吞噬作用没有抑制活性。当这些BAL液样品与伴刀豆球蛋白A-琼脂糖珠孵育时，其抑制活性也丧失，表明抑制剂是一种糖蛋白。通过排阻过滤估计抑制剂大于100，000 Da。在与伴刀豆球蛋白A-琼脂糖珠结合后，BAL液样品和卡氏肺孢子虫裂解物中的抑制剂可以用200 mM甲基甘露糖洗脱。用针对卡氏肺孢子虫主要表面糖蛋白的抗体处理粗制BAL液样品和卡氏肺孢子虫裂解物以及200 mM甲基甘露糖醇消除了它们的抑制活性。这些结果表明，能够抑制肺泡巨噬细胞吞噬活性的因子是卡氏肺孢子虫主要表面糖蛋白或其一种或多种衍生物。
Alveolar macrophages from Pneumocystis carinii-infected rats are defective in phagocytosis. To investigate whether this defect is due to a certain factor present in P. carinii-infected lungs, alveolar macrophages from uninfected rats were incubated with bronchoalveolar lavage (BAL) fluid samples from P. carinii-infected rats. Alveolar macrophages treated with these BAL fluid samples became defective in phagocytosis but remained normal when treated with BAL fluid samples from noninfected or Toxoplasma gondii-infected rats. The suppressive activity of the BAL fluid samples from P. carinii-infected rats on phagocytosis was retained when the BAL fluid samples were passed through a filter with a pore size of 0.45 mum but was lost when the BAL fluid samples were digested with proteases such as trypsin, pepsin, papain, or endopeptidase Gly-C. Lipid fractions of these BAL fluid samples had no suppressive activity on phagocytosis. The suppressive activity of these BAL fluid samples was also lost when they were incubated with concanavalin A-agarose beads, suggesting that the inhibitor is a glycoprotein. The inhibitor was estimated to be larger than 100,000 Da by exclusion filtration. After binding to the concanavalin A-agarose beads, the inhibitor in BAL fluid samples and P. carinii lysate could be eluted with 200 mM methylmannose. Treatment of both the crude BAL fluid samples and P. carinii lysate and the 200 mM methylmannose eluate with antibody against the major surface glycoprotein of P. carinii eliminated their suppressive activity. These results suggest that the factor capable of suppressing the phagocytic activity of alveolar macrophages is P. carinii major surface glycoprotein or one or more of its derivatives.