Endotoxin suppresses expression of apoprotein E by mouse macrophages in vivo and in culture: a biochemical and genetic study

Journal Article · Sat Sep 10 04:00:00 EDT 1983 · J. Biol. Chem.; (United States)

OSTI ID:6133658

Werb, Z; Chin, J R

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 and apo-E synthesis in culture were selective, and secretion of many other major macrophage proteins was not affected. When then LPS-elicited macrosphages 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 E/sub 2/ synthesis, prostaglandin E/sub 2/ itself did not suppress apo-E synthesis. Macrophages from C3H/HeJ (Lps/sup d//Lps/sup d/) mice, which are resistant to LPS, were neither primed for H/sub 2/O/sub 2/ production nor suppressed for apo-E synthesis in response to LPS in vivo (30 ..mu..g/mouse) or in culture (1..mu../ml), whereas macrophages from the co-isogenic C3H/HeN (Lps/sup n//Lps/sup n/) strain were induced for H/sub 2/O/sub 2/ 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.

• Research Organization: Univ. of California, San Francisco
• DOE Contract Number: AC03-76SF01012
• OSTI ID: 6133658
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 258:17; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
ANTIGENS
BACTERIA
BACTERIOPHAGES
BIOASSAY
BIOSYNTHESIS
BODY
BONE MARROW
CARBOHYDRATES
CELL CULTURES
ENDOTOXINS
HEMATOPOIETIC SYSTEM
IMMUNE REACTIONS
IMMUNOSUPPRESSION
IN VIVO
INHIBITION
LIPIDS
LIPOPOLYSACCHARIDES
MAMMALS
MATERIALS
MEMBRANES
METABOLISM
MICE
MICROORGANISMS
ORGANIC COMPOUNDS
ORGANS
PARASITES
PERITONEUM
POLYSACCHARIDES
PROTEINS
RODENTS
SACCHARIDES
SECRETION
SEROUS MEMBRANES
SYNTHESIS
TISSUES
TOXIC MATERIALS
TOXINS
VERTEBRATES
VIRUSES