Dose-dependent inhibitory effect of CD47 in macrophage uptake of IgG-opsonized murine erythrocytes
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Published on: December 3, 2020
Mattias Olsson1, Anna Nilsson, Per-Arne Oldenborg
1Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden. mattias.olsson@histocel.umu.se
Abstract:
The cell surface glycoprotein CD47 on target cells can bind to the inhibitory receptor SIRPalpha on macrophages to inhibit phagocytosis of antibody sensitized blood cells. The aim of this study was to determine if CD47 dose-dependently can regulate macrophage uptake of IgG-opsonized RBCs. CD47(+/-) RBCs express about 50% of the CD47 level found on CD47(+/+) RBCs. When injected into CD47(+/+) mice, CD47(+/-) RBCs showed a significantly faster antibody-mediated clearance as compared with CD47(+/+) RBCs injected into the same recipient. In vitro phagocytosis experiments confirmed that CD47(+/-) RBCs were taken up significantly more than CD47(+/+) RBCs, but significantly less than CD47(-/-) RBCs. A reduction in RBC CD47 expression just below 50% of that in normal RBCs can significantly accelerate RBC clearance by macrophages in the presence of RBC autoantibodies. This may have relevance for transfusion of stored RBCs, where loss of CD47 is seen over time, and in clearance of these cells by antibody-dependent phagocytosis.
Insights
Reduced CD47 glycoprotein on red blood cells (RBCs) significantly accelerates their clearance by macrophages, especially with autoantibodies. This impacts RBC transfusion and antibody-dependent phagocytosis.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- CD47 on target cells binds SIRPalpha on macrophages, inhibiting phagocytosis of antibody-sensitized blood cells.
- Understanding CD47's role is crucial for managing antibody-mediated clearance of blood cells.
Purpose of the Study:
- To investigate the dose-dependent regulation of macrophage uptake of IgG-opsonized RBCs by CD47.
- To determine the impact of reduced CD47 expression on RBC clearance in vivo and in vitro.
Main Methods:
- In vivo studies involved injecting CD47(+/-) and CD47(+/+) RBCs into CD47(+/+) mice.
- In vitro experiments assessed phagocytosis of RBCs with varying CD47 expression levels.
- Flow cytometry was used to quantify CD47 expression on RBCs.
Main Results:
- CD47(+/-) RBCs exhibited significantly faster antibody-mediated clearance in vivo compared to CD47(+/+) RBCs.
- In vitro, CD47(+/-) RBCs were phagocytosed more than CD47(+/+) RBCs but less than CD47(-/-) RBCs.
- A reduction in RBC CD47 expression below 50% accelerated clearance in the presence of autoantibodies.
Conclusions:
- CD47 dose-dependently regulates macrophage uptake of IgG-opsonized RBCs.
- Reduced CD47 expression significantly enhances RBC clearance by macrophages, particularly with autoantibodies.
- Findings are relevant for RBC transfusion safety and understanding antibody-dependent phagocytosis of aged or altered RBCs.
