Modulation of murine hepatic lipase activity by exogenous and endogenous Kupffer-cell activation.
Deficiency of hepatic lipase (HL) may play a role in the lipoprotein abnormalities in chronic inflammatory states which are characterized by reticuloendothelial-system activation and cytokine release. HL triacylglycerol hydrolase activity was measured in heparin perfusates of livers from autoimmune MRL/lpr mice, which spontaneously develop a condition closely resembling human lupus erythematosis and exhibit spontaneous Kupffer-cell activation after 8 weeks of age, as well as from normal mice treated with Corynebacterium parvum or polyinosinic-polycytidylic acid complex [poly(I.C)] to induce Kupffer-cell activation. HL activity in MRL/lpr mice older than 8 weeks was 29.5% (P = 0.002) of that in age-matched control MRL/++ mice. Treatment of normal mice with C. parvum or poly(I.C) resulted in HL activities 18.6% (P = 0.004) and 13.1% (P = 0.007) respectively of untreated controls. Northern-blot hybridization of liver poly(A)+ RNA showed no differences in HL mRNA abundance in MRL/++ mice compared with the MRL/lpr autoimmune strain after 8 weeks of age, or in normal control mice compared with those treated with C. parvum, indicating attenuation of HL activity at the translational or post-translational level. Deficiency of this enzyme may represent one of the mechanisms contributing to the dyslipoproteinaemia of autoimmune disease and chronic infection.
Magilavy
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DB
Department of Pediatrics, University of Chicago, La Rabida Hospital, IL 60637.
Zhan
R
R
Black
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DD
D000818:Animals; D005260:Female; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008262:Macrophage Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010477:Perfusion; D011425:Propionibacterium acnes; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D008049:Lipase