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The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia
Francesca Granucci1, Filippo Petralia, Matteo Urbano
1Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy.
Abstract:
Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation.
Insights
The Macrophage receptor with collagenous structure (MARCO) regulates actin cytoskeleton changes and reduces antigen uptake during dendritic cell (DC) and microglial cell maturation. MARCO expression is key for these functional and morphological shifts in immune cells.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor found on specific macrophage populations.
- MARCO mRNA is upregulated in splenic dendritic cells (DCs) and microglial cells upon activation.
- MARCO's role in DC and microglial maturation was previously unclear.
Purpose of the Study:
- To investigate the function of MARCO in the maturation of splenic DCs and microglial cells.
- To determine the effect of MARCO expression on actin cytoskeleton organization and antigen uptake.
- To elucidate the role of MARCO in immune cell morphology and function.
Main Methods:
- Global gene expression analysis to identify MARCO upregulation.
- Studying MARCO expression in splenic DCs and microglial cells post-activation.
- Observing actin cytoskeleton organization in DCs and microglia with varying MARCO levels.
- Performing MARCO transfection and knockdown experiments in DCs.
- Assessing antigen internalization capacity in DCs and microglial cells.
Main Results:
- MARCO expression on splenic DCs correlates with significant actin cytoskeleton rearrangements.
- MARCO expression induces a mature DC phenotype, characterized by nonadherence and altered actin distribution.
- MARCO knockdown in DCs prevents the acquisition of a mature phenotype.
- MARCO expression is associated with decreased antigen uptake in DCs and microglial cells.
Conclusions:
- MARCO plays a crucial role in regulating actin cytoskeleton dynamics during DC and microglial maturation.
- MARCO expression contributes to the down-regulation of antigen uptake function in mature immune cells.
- MARCO is a key regulator of immune cell maturation, influencing both morphology and function.
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