Endotoxin suppresses expression of apoprotein E by mouse macrophages in vivo and in culture. A biochemical and genetic study.
We have observed that the synthesis and secretion of apo-E, a component of plasma lipoproteins, are suppressed in mouse macrophages exposed to bacterial lipopolysaccharide endotoxin (LPS) in culture or in vivo. Control mouse macrophages contained intracellular immunofluorescent apo-E, and apo-E represented about 10% of secreted protein. After intraperitoneal injection of LPS, freshly lavaged macrophages neither contained intracellular apo-E nor secreted apo-E. The suppressive effects of LPS on apo-E synthesis in culture were selective, and secretion of many other major macrophage proteins was not affected. When the LPS-elicited macrophages were cultured for 24-72 h in the absence of LPS, synthesis of apo-E was initiated. Treatment of bone marrow-derived or peritoneal macrophages in culture with less than 1 ng of LPS/ml inhibited apo-E synthesis and secretion by 18 h of treatment. Although LPS stimulates prostaglandin E2 synthesis, prostaglandin E2 itself did not suppress apo-E synthesis. Macrophages from C3H/HeJ (Lpsd/Lpsd) mice, which are resistant to LPS, were neither primed for H2O2 production nor suppressed for apo-E synthesis in response to LPS in vivo (30 micrograms/mouse) or in culture (1 microgram/ml), whereas macrophages from the co-isogenic C3H/HeN (Lpsn/Lpsn) strain were induced for H2O2 secretion and had suppressed synthesis of apo-E. Because apo-E serves as a recognition determinant for the receptor-mediated clearance of lipoproteins, the decreased synthesis of apo-E after LPS treatment may in part explain the hyperlipoproteinemia associated with endotoxins in vivo.
D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis* / Q000235:genetics; D001057:Apolipoproteins E; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H
D001053:Apolipoproteins; D001057:Apolipoproteins E; D008070:Lipopolysaccharides