CD36 is not involved in scavenger receptor-mediated endocytic uptake of glycolaldehyde- and methylglyoxal-modified proteins by liver endothelial cells.
Circulating proteins modified by advanced glycation end-products (AGE) are mainly taken up by liver endothelial cells (LECs) via scavenger receptor-mediated endocytosis. Endocytic uptake of chemically modified proteins by macrophages and macrophage-derived cells is mediated by class A scavenger receptor (SR-A) and CD36. In a previous study using SR-A knockout mice, we demonstrated that SR-A is not involved in endocytic uptake of AGE proteins by LECs [Matsumoto et al. (2000) Biochem. J. 352, 233-240]. The present study was conducted to determine the contribution of CD36 to this process. Glycolaldehyde-modified BSA (GA-BSA) and methylglyoxal-modified BSA (MG-BSA) were used as AGE proteins. 125I-GA-BSA and 125I-MG-BSA underwent endocytic degradation by these cells at 37 degrees C, and this process was inhibited by several ligands for the scavenger receptors. However, this endocytic uptake of 125I-GA-BSA by LECs was not inhibited by a neutralizing anti-CD36 antibody. Similarly, hepatic uptake of (111)In-GA-BSA after its intravenous injection was not significantly attenuated by co-administration of the anti-CD36 antibody. These results clarify that CD36 does not play a significant role in elimination of GA-BSA and MG-BSA from the circulation, suggesting that the receptor involved in endocytic uptake of circulating AGE proteins by LEC is not SR-A or CD36.
Nakajou
Keisuke
K
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973.
Horiuchi
Seikoh
S
Sakai
Masakazu
M
Hirata
Kenshiro
K
Tanaka
Makiko
M
Takeya
Motohiro
M
Kai
Toshiya
T
Otagiri
Masaki
M
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal; D018955:CD36 Antigens / Q000276:immunology / Q000502:physiology*; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019301:Oleic Acid / Q000378:metabolism; D011765:Pyruvaldehyde / Q000737:chemistry*; D051381:Rats; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D017127:Glycation End Products, Advanced; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D012710:Serum Albumin, Bovine; D019301:Oleic Acid; D011765:Pyruvaldehyde; D000079:Acetaldehyde; C010972:glycolaldehyde