Lipoproteins inhibit macrophage activation by lipoteichoic acid

Regulation of lipid metabolism during infection is thought to be part of ho st defense, as lipoproteins neutralize endotoxin (LPS) and viruses. Gram-po sitive infections also induce disturbances in lipid metabolism. Therefore, we investigated whether lipoproteins could inhibit the toxic effects of lip oteichoic acid (LTA), a fragment of gram-positive bacteria. LTA activated R AW264.7 macrophage cells, stimulating production of tumor necrosis factor ( TNF) in a dose-dependent matter, but produced less TNF than that seen after LPS activation. High density (HDL) or low density lipoprotein (LDL) alone inhibited the ability of LPS to stimulate TNF production, but had little ef fect on the activation by LTA, When a maximally effective dose of LTA was m ixed with lipoproteins and 10% lipoprotein-depleted plasma (LPDP), the abil ity of LTA to stimulate macrophage production of TNF was inhibited. HDL, LD L, and the synthetic particle, Soyacal, when mixed with LPDP, were able to inhibit the ability of LTA to activate macrophages, Lipopolysaccharide-bind ing protein (LBP) substituted for LPDP in catalyzing lipoprotein neutraliza tion of LTA by HDL, Antibody to LBP inhibited the ability of LPDP to induce LTA neutralization by HDL. Thus, lipoproteins can prevent macrophage activ ation by fragments from both gram-positive and gram-negative microorganisms .