Effects of scavenger receptors-1 class A stimulation on macrophage morphology and highly modified advanced glycation end product-protein phagocytosis.

Abstract

Advanced glycation end-products (AGEs), which comprise non-enzymatically glycosylated proteins, lipids, and nucleic acid amino groups, play an important role in several diseases and aging processes including angiopathy, renal failure, diabetic complications, and neurodegenerative diseases. Among AGE-associated phenotypes, toxic AGEs, glyceraldehyde-derived AGE-2, and glycolaldehyde-derived AGE-3 are involved in the pathogenesis of diabetic complications. In addition, macrophages are reported to remove extracellular AGEs from tissues via scavenger receptors, leading to the progression of atherosclerosis. In the present study, we found that AGE-2 and AGE-3 enhanced their own endocytic uptake by RAW264.7 mouse macrophage-like cells in a concentration-dependent manner. Furthermore, we demonstrated, for the first time, the morphology of phagocytic macrophages and the endocytosis of AGE particles. The toxic AGEs induced the expression of a scavenger receptor, CD204/scavenger receptors-1 class A (SR-A). Notably, an antibody against CD204 significantly prevented toxic AGE uptake. Moreover, an SR-A antagonistic ligand, fucoidan, also attenuated the AGE-2- and AGE-3-evoked uptake in a concentration-dependent manner. These results indicated that SR-A stimulation, at least in part, plays a role in AGE uptake.

• Authors: Shinichi Hamasaki, Takuro Kobori, Yui Yamazaki, Atsuhiro Kitaura, Atsuko Niwa, Takashi Nishinaka, Masahiro Nishibori, Shuji Mori, Shinichi Nakao, Hideo Takahashi
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 5901 (04 12 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29651042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Glycation End Products, Advanced
• Msr1 protein, mouse
• Polysaccharides
• Scavenger Receptors, Class A
• Glyceraldehyde
• fucoidan
• Acetaldehyde
• glycolaldehyde

Topics

• Acetaldehyde (analogs & derivatives, metabolism)
• Animals
• Antibodies, Neutralizing (pharmacology)
• Endocytosis (drug effects)
• Gene Expression Regulation
• Glycation End Products, Advanced (agonists, genetics, immunology)
• Glyceraldehyde (metabolism)
• Mice
• Phagocytosis (drug effects)
• Polysaccharides (pharmacology)
• Protein Processing, Post-Translational
• RAW 264.7 Cells
• Scavenger Receptors, Class A (antagonists & inhibitors, genetics, immunology)