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.
Department of Pediatrics, University of Chicago, La Rabida Hospital, IL 60637.
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Magilavy
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Zhan
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Black
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