Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D
Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D
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DOI：
10.1067/mlc.2001.115220
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发表时间：
2001-06-01
期刊：
影响因子：
--
通讯作者：
Beers, MF
中科院分区：
文献类型：
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作者：
Atochina, EN;Beck, JM;Beers, MF
肺表面活性蛋白SP-A和SP-D是肺凝集素家族的成员，在肺宿主防御中起重要作用。这两种蛋白选择性地与卡氏肺孢子虫（Pneumocystis carinii，PC）结合，并调节该病原体与肺泡巨噬细胞的相互作用。将PC微生物（2 × 10（5））接种到不需要类固醇进行免疫抑制的C.B-17 scid/scid小鼠体内。接种4周后，支气管肺泡灌洗液（BAL）被分成三个部分-细胞团，大聚集体（LA），和小聚集体（SA）表面活性剂-和每个部分进行了分析的表面活性剂成分的表达。在未感染的小鼠中，发现大多数SP-A（62% +/- 10%）与LA组分中的脂质相关，而55% +/- 14%的SP-D分布在SA组分中。与此相反，疏水蛋白SP-B和SP-C都只与LA相关，PC感染导致所有表面活性成分表达的重大变化。感染PC后LA的总蛋白含量无明显变化（对照组的115% +/- 18%），而SA蛋白含量显著增加（对照组的240% ± 18%，P <0.001），与此相反，LA的磷脂含量显著降低（对照水平的53% ± 5%，P < .001），而感染小鼠的SA磷脂含量增加（对照水平的172% ± 16%，P < .001）。通过蛋白质印迹，PC肺炎（PCP）诱导总肺泡SP-D蛋白增加3倍，这主要反映在SA SP-D的增加（对照的454% +/-135%，P <0.05）。PCP中肺泡SP-A蛋白总含量也增加，因为SA中SP-A大量增加（对照组的720% +/-115%，P <0.05）; LA中SP-A水平无变化。肺聚集蛋白表达的增加是选择性的，因为PCP导致LA中SP-B和SP-C的下调（分别为对照的5% +/-2%和13% +/-2%，P <0.001）。我们的结论是，PCP诱导肺泡聚集素水平的显着升高，因为SA表面活性剂中SP-A和SP-D蛋白的表达和积累增加。
Surfactant proteins SP-A and SP-D, members of the collectin family, have been shown to play a significant role in lung host defense, Both proteins selectively bind Pneumocystis carinii (PC) organisms and modulate the interaction of this pathogen with alveolar macrophages, We hypothesized that the expression and distribution of lung collectins SP-A and SP-D is altered by PC lung infection. PC organisms (2 x 10(5)) were inoculated intratracheally into C.B-17 scid/scid mice that do not require steroids for immunosuppression. Four weeks after inoculation, bronchoalveolar lavage (BAL) fluid was fractionated into three fractions-cell pellet, large aggregate (LA), and small aggregate (SA) surfactant-and each fraction was analyzed for the expression of surfactant components. In uninfected mice, the majority of SP-A (62% +/- 10%) was found in association with lipids in the LA fraction, while 55% +/- 14% of SP-D was distributed in the SA fraction. In contrast, both hydrophobic proteins SP-B and SP-C were associated exclusively with LA, PC infection resulted in major changes in the expression of all surfactant components. Total protein content of LA was unchanged by PC infection (115% +/- 18% of control), whereas SA protein content markedly increased (240% +/- 18% of control level, P < .001), In contrast, the phospholipid content of LA was significantly decreased (53% +/- 5% of control level, P < .001), whereas the SA phospholipid content of infected mice was increased (172% +/- 16% of control level, P < .001). By Western blotting, PC pneumonia (PCP) induced a 3-fold increase in the total alveolar SP-D protein that was reflected mainly in increases in SA SP-D (454% +/- 135% of control, P < .05). The total alveolar SP-A protein content was also increased in PCP because of a large increase in SP-A in SA (720% +/- 115% of control, P < .05); SP-A levels in LA were unchanged. The increases in lung collectin expression were selective, because PCP resulted in the down-regulation of both SP-B and SP-C in LA (5% +/- 2% and 13% +/- 2% of control, respectively, P < .001). We conclude that PCP induces marked elevations in alveolar collectin levels because of increased expression and accumulation of SP-A and SP-D protein in SA surfactant.