Enhanced degradation of high density lipoprotein by peritoneal macrophages from nude mice is attenuated by interleukin-1.
Athymic nude mice are characterized by deficient cellular immunity due to almost complete absence of functional mature T-lymphocytes. Plasma HDL (the major cholesterol carrier in mice) cholesterol levels in nude mice were found to be reduced by 1.7 fold in comparison to control Balb/c mice. Cellular degradation of HDL by peritoneal macrophages (MPM) that were obtained from nude mice, was 2.5 fold greater in comparison to MPM obtained from Balb/c mice. Since nude mice lack cytokines that can affect lipid metabolism, intravenous administration of 10 micrograms/100g body weight of interleukin-1 (IL-1), tumor necrosis factor (TNF), or transforming growth factor (TGF) on HDL degradation by their PM, were investigated. IL-1 (but not TNF) reduced HDL (50 micrograms of protein/ml) cellular degradation from 810 +/- 34 to 350 +/- 12 ng/mg cell protein (p < 0.01) in nude mice. In control Balb/c mice, however, IL-1 as well as TNF enhanced macrophage degradation of HDL by 56% and 280%, respectively. TGF injection into nude mice (but not control mice) decreased HDL degradation by their MPM by 50%. We, thus, suggest that in nude mice the reduced plasma and HDL cholesterol levels are probably due to increased HDL degradation, which may be secondary to IL-1 and TGF deficiency.
Keidar
S
S
Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel.
Gilhar
A
A
Kaplan
M
M
Brook
J G
JG
Aviram
M
M
D000818:Animals; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013047:Specific Pathogen-Free Organisms; D015291:Transforming Growth Factors / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008076:Cholesterol, HDL; D007375:Interleukin-1; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D015291:Transforming Growth Factors; D002784:Cholesterol