Acute inflammation increases selective uptake of HDL cholesteryl esters into adrenals of mice overexpressing human sPLA2.
The acute-phase protein secretory phospholipase A2 (sPLA2) 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 sPLA2 enhances the selective uptake of HDL into the adrenals in response to acute inflammation as a possible physiological role for the sPLA2-HDL interaction. Human sPLA2-transgenic mice, in which sPLA2 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 sPLA2-transgenic mice (-18%, P < 0.05) but remained unchanged in wild-type mice. The fractional catabolic rates of both 125I-labeled tyraminecellobiose (TC)-HDL and [3H]cholesteryl ether increased significantly in the sPLA2-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). sPLA2-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%/ micro g tissue protein, P < 0.001). In summary, upregulation of sPLA2 expression during the APR specifically increases the selective uptake of HDL cholesteryl ester into the adrenals. These data suggest a novel metabolic role for sPLA2: modification of HDL during the APR to promote increased adrenal uptake of HDL cholesteryl ester to serve as source for steroid hormone synthesis.
Tietge
Uwe J F
UJ
Univ. of Pennsylvania Medical Center, 654 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA. rader@mail.med.upenn.edu
Maugeais
Cyrille
C
Cain
Willliam
W
Rader
Daniel J
DJ
D000210:Acute-Phase Reaction; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008822:Mice, Transgenic; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism*; D054467:Phospholipases A2; D014316:Tritium
D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D014316:Tritium; D010741:Phospholipases A; D054467:Phospholipases A2