Acute inflammation increases selective uptake of HDL cholesteryl esters into adrenals of mice overexpressing human sPLA2

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.