Acute inflammation increases selective uptake of HDL cholesteryl esters into adrenals of mice overexpressing human sPLA2
Acute inflammation increases selective uptake of HDL cholesteryl esters into adrenals of mice overexpressing human sPLA2
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DOI：
10.1152/ajpendo.00576.2002
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发表时间：
2003-08-01
影响因子：
5.1
通讯作者：
Rader, DJ
中科院分区：
文献类型：
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作者：
Tietge, UJF;Maugeais, C;Rader, DJ
急性期蛋白分泌磷脂酶A(2) （sPLA(2)）影响高密度脂蛋白（HDL）的代谢。众所周知，肾上腺利用高密度脂蛋白胆固醇作为固醇的来源。本研究的目的是验证sPLA(2)在急性炎症反应中增强肾上腺对HDL的选择性摄取这一假设，这可能是sPLA(2)-HDL相互作用的生理作用。我们使用了sPLA(2)转基因小鼠，其中sPLA(2)的表达在炎症刺激下上调。注射细菌脂多糖（LPS）诱导急性期反应（APR） 10小时后，sPLA(2)转基因小鼠血浆HDL胆固醇水平显著下降（- 18%,P < 0.05），而野生型小鼠血浆HDL胆固醇水平保持不变。APR诱导后，i -125标记的酪胺-纤维素二糖(TC)- hdl和[h -3]胆固醇醚的分数分解代谢率在sPLA(2)转基因小鼠中显著升高（分别为0.18 +/- 0.01比0.21 +/- 0.01池/ h， P < 0.05，和0.31 +/- 0.02比0.42 +/- 0.05池/ h， P < 0.05），而在野生型小鼠中保持不变（分别为0.10 +/- 0.01比0.22 +/- 0.02池/ h）。APR诱导后，两组大鼠肝脏对HDL全颗粒的摄取均增加（P < 0.001）。在APR诱导后，sPLA(2)转基因小鼠的肾上腺选择性摄取比野生型小鼠高2.4倍（156 +/- 6比65 +/- 5%/杯组织蛋白，P < 0.001）。总之，在APR期间sPLA(2)表达的上调特异性地增加了HDL胆固醇酯进入肾上腺的选择性摄取。这些数据表明sPLA具有一种新的代谢作用(2)：在APR期间改变HDL，促进肾上腺对HDL胆固醇酯的摄取增加，从而作为类固醇激素合成的来源。
The acute-phase protein secretory phospholipase A(2) ( sPLA(2)) influences the metabolism of high-density lipoproteins (HDL). The adrenals are known to utilize HDL cholesterol as a source of sterols. The aim of the present study was to test the hypothesis that sPLA(2) enhances the selective uptake of HDL into the adrenals in response to acute inflammation as a possible physiological role for the sPLA(2)-HDL interaction. Human sPLA(2)-transgenic mice, in which sPLA(2) expression is upregulated by inflammatory stimuli, were used. Ten hours after induction of the acute-phase response (APR) by injection of bacterial lipopolysaccharide (LPS), plasma levels of HDL cholesterol decreased significantly in sPLA(2)-transgenic mice ( - 18%, P < 0.05) but remained unchanged in wild-type mice. The fractional catabolic rates of both I-125-labeled tyramine-cellobiose (TC)-HDL and [H-3] cholesteryl ether increased significantly in the sPLA(2)-transgenic mice after induction of the APR (0.18 +/- 0.01 vs. 0.21 +/- 0.01 pool/ h, P < 0.05, and 0.31 +/- 0.02 vs. 0.42 +/- 0.05 pool/ h, P < 0.05, respectively) but remained unchanged in the wild- type mice ( 0.10 +/- 0.01 vs. 0.22 +/- 0.02 pool/ h, respectively). After induction of the APR, in both groups HDL holoparticle uptake by the liver was increased ( P < 0.001). sPLA(2)-transgenic mice had 2.4-fold higher selective uptake into the adrenals after induction of the APR than wild- type mice ( 156 +/- 6 vs. 65 +/- 5%/ mug tissue protein, P < 0.001). In summary, upregulation of sPLA(2) expression during the APR specifically increases the selective uptake of HDL cholesteryl ester into the adrenals. These data suggest a novel metabolic role for sPLA(2): modification of HDL during the APR to promote increased adrenal uptake of HDL cholesteryl ester to serve as source for steroid hormone synthesis.