Acute inflammation increases the selective uptake of HDL-cholesteryl esters into adrenals of mice overexpressing human secretory phospholipase A2

2 ABSTRACT The acute phase protein secretory phospholipase A2 (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 physiologic role for the sPLA 2 HDL interaction. Human sPLA 2 transgenic mice , in which sPLA 2 expression is upregulated by inflammatory stimuli, were used. 10 h 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 wildtype mice. The fractional catabolic rates of both 125 I-tyramine-cellobiose(TC)-HDL and 3 H-cholesteryl ether increased significantly in the sPLA 2 transgenic mice after induction of the 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 wildtype mice (156 ± 6 vs. 65 ± 5 %/µg 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.