The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia.
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.
Granucci
Francesca
F
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy.
Petralia
Filippo
F
Urbano
Matteo
M
Citterio
Stefania
S
Di Tota
Francesco
F
Santambrogio
Laura
L
Ricciardi-Castagnoli
Paola
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism; D002455:Cell Division; D003599:Cytoskeleton / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D015536:Down-Regulation; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B; D013696:Temperature; D013997:Time Factors; D015854:Up-Regulation
D000199:Actins; D000941:Antigens; D018076:DNA, Complementary; D008070:Lipopolysaccharides; C092228:Marco protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor