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/1pr 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/1pr 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/1pr 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.