Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A.
Type 2 diabetes (T2D) is associated with accelerated atherosclerosis, which accounts for approximately 75% of all diabetes-related deaths. Here we investigate the link between diabetes and macrophage cholesteryl ester accumulation. When diabetic (db/db) mice are given cholesteryl ester intraperitoneally (IP), peritoneal macrophages (PerMPhis) recovered from these animals showed a 58% increase in intracellular cholesteryl ester accumulation over PerMPhis from heterozygote control (db/+) mice. Notably, PerMPhi fluid-phase endocytosis and large particle phagocytosis was equivalent in db/+and db/db mice. However, IP administration of CD36 and SR-A blocking antibodies led to 37% and 25% reductions in cholesteryl ester accumulation in PerMPhi. Finally, in order to determine if these scavenger receptors (SRs) were part of the mechanism responsible for the increased accumulation of cholesteryl esters observed in the diabetic mouse macrophages, receptor expression was quantified by flow cytometry. Importantly, db/db PerMPhis showed a 43% increase in CD36 expression and an 80% increase in SR-A expression. Taken together, these data indicate that direct cholesteryl ester accumulation in mouse macrophages is mediated by CD36 and SR-A, and the magnitude of accumulation is increased in db/db macrophages due to increased scavenger receptor expression.
Guest
Christopher B
CB
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Hartman
Matthew E
ME
O'Connor
Jason C
JC
Chakour
Kenneth S
KS
Sovari
Ali A
AA
Freund
Gregory G
GG
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D004705:Endocytosis; D005434:Flow Cytometry; D007328:Insulin / Q000097:blood; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010587:Phagocytosis; D051117:Scavenger Receptors, Class A / Q000378:metabolism*
D001786:Blood Glucose; D018955:CD36 Antigens; D002788:Cholesterol Esters; D007328:Insulin; D051117:Scavenger Receptors, Class A