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G P Ma

Publications and source records attributed to G P Ma.

3 recordsLinked to original sources
PubMed1990

Oxidized low density lipoprotein suppresses the expression of tumor necrosis factor-alpha mRNA in stimulated murine peritoneal macrophages.

In the present report we have examined expression of the gene encoding the inflammatory monokine TNF-alpha in murine peritoneal macrophages treated with different forms of low density lipoprotein (LDL). LDL modified by oxidation in vitro is unable to stimulate inflammatory gene expression in peritoneal macrophages. However, treatment of macrophage cultures with oxidized LDL for 6 h or more resulted in a concentration and time-dependent suppression of TNF-alpha mRNA expression induced in response to stimulation with either LPS or maleylated BSA. This suppression was maximal after 12 h of exposure to oxidized LDL and at a concentration of 100 to 200 micrograms LDL cholesterol/ml of culture medium. The suppressive effect was restricted to oxidatively modified LDL as treatment with native LDL or acetylated LDL did not affect TNF-alpha mRNA expression, despite the fact that both acetylated and oxidized LDL lead to intracellular lipid accumulation. The expression of maleyl albumin-stimulated TNF-alpha mRNA expression could be reproduced by lipid extracts of oxidized LDL provided to macrophages at the same cholesterol concentration as from the intact lipoprotein particle. Extracts from native LDL were ineffective. These results suggest that oxidized lipid accumulation in monocytes infiltrating the arterial wall may lead to the suppression of certain inflammatory functions which, in turn, may influence the development of mature atherosclerotic lesions.

Acetylation↗
PubMed1990

Intercellular transport of lysosomal acid lipase mediates lipoprotein cholesteryl ester metabolism in a human vascular endothelial cell-fibroblast coculture system.

We present results from studies of human cell culture models to support the premise that the extracellular transport of lysosomal acid lipase has a function in lipoprotein cholesteryl ester metabolism in vascular tissue. Vascular endothelial cells secreted a higher fraction of cellular acid lipase than did smooth muscle cells and fibroblasts. Acid lipase and lysosomal beta-hexosaminidase were secreted at approximately the same rate from the apical and basolateral surface of an endothelial cell monolayer. Stimulation of secretion with NH4Cl did not affect the polarity. We tested for the ability of secreted endothelial lipase to interact with connective tissue cells and influence lipoprotein cholesterol metabolism in a coculture system in which endothelial cells on a micropore filter were suspended above a monolayer of acid lipase-deficient (Wolman disease) fibroblasts. After 5-7 d, acid lipase activity in the fibroblasts reached 10%-20% of the level in normal cells; cholesteryl esters that had accumulated from growth in serum were cleared. Addition of mannose 6-phosphate to the coculture medium blocked acid lipase uptake and cholesterol clearance, indicating that lipase released from endothelial cells was packaged into fibroblast lysosomes by a phosphomannosyl receptor-mediated pathway. Supplementation of the coculture medium with serum was not required for lipase uptake and cholesteryl ester hydrolysis by the fibroblasts, but was necessary for cholesterol clearance. Results from our coculture model suggest that acid lipase may be transported from intact endothelium to cells in the lumen or the wall of a blood vessel. We postulate that delivery of acid hydrolases and lipoproteins to a common endocytic compartment may occur and have an impact on cellular lipoprotein processing.

Biological Transport↗