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Macrophages lacking scavenger receptor A show a decrease in binding and uptake of acetylated low-density lipoprotein
V Terpstra1, N Kondratenko, D Steinberg
1Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0682, USA.
Abstract:
Macrophage binding of oxidatively damaged red blood cells (OxRBC) and apoptotic thymocytes correlates in many instances with a loss of phospholipid bilayer asymmetry, i.e., with an increase in expression of phosphatidylserine on the outer leaflet of the plasma membrane. Oxidatively modified LDL (OxLDL) can compete for the binding of these ligands to macrophages. However, the receptor(s) responsible remains to be identified. The present studies show that mouse peritoneal macrophages totally lacking scavenger receptor A (SRA) bound OxRBC just as effectively as wild-type macrophages, whereas their binding and uptake of acetyl LDL was reduced by more than 80%. Binding of apoptotic thymocytes and binding of OxLDL were also reduced, but only by 20-30%. We conclude that SRA is not involved in the recognition of phosphatidylserine-rich membranes but contributes to the binding of OxLDL and apoptotic thymocytes. The binding of OxRBC was almost totally calcium-dependent, whereas the binding of apoptotic thymocytes was not, suggesting that the mechanisms involved in their uptake by macrophages under these conditions were different.
Insights
Scavenger Receptor A (SRA) does not bind phosphatidylserine-rich cells like oxidatively damaged red blood cells (OxRBC). SRA mediates uptake of oxidized LDL (OxLDL) and apoptotic thymocytes by macrophages.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophage recognition of damaged cells involves phosphatidylserine exposure.
- Oxidized low-density lipoprotein (OxLDL) can compete with other ligands for macrophage binding.
- The specific receptors mediating these interactions are not fully identified.
Purpose of the Study:
- To investigate the role of Scavenger Receptor A (SRA) in macrophage binding and uptake of oxidatively damaged red blood cells (OxRBC), apoptotic thymocytes, and OxLDL.
- To elucidate the receptor mechanisms involved in the clearance of phosphatidylserine-exposing cells.
Main Methods:
- Utilized scavenger receptor A knockout (SRA-KO) mice and wild-type (WT) mice.
- Assessed macrophage binding and uptake of OxRBC, acetylated LDL (acetyl LDL), and OxLDL.
- Analyzed calcium dependence of ligand binding.
Main Results:
- SRA-KO macrophages exhibited similar binding of OxRBC compared to WT macrophages.
- Binding and uptake of acetyl LDL by SRA-KO macrophages were reduced by over 80%.
- Binding of apoptotic thymocytes and OxLDL was reduced by 20-30% in SRA-KO macrophages.
- OxRBC binding was calcium-dependent, while apoptotic thymocyte binding was not.
Conclusions:
- Scavenger Receptor A (SRA) is not essential for recognizing phosphatidylserine-rich membranes on OxRBC.
- SRA significantly contributes to the uptake of OxLDL and apoptotic thymocytes by macrophages.
- Distinct calcium-dependent and independent mechanisms mediate the recognition of OxRBC and apoptotic thymocytes, respectively.