Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins.
Deletion of apoptotic cells from tissues involves their phagocytosis by macrophages, dendritic cells, and tissue cells. Although much attention has been focused on the participating ligands, receptors, and mechanisms of uptake, little is known of the disposition of the ingested cell within the phagosome. Here we show that uptake of apoptotic cells by macrophages or fibroblasts results in rapid phagosome maturation, whereas macrophage phagosomes containing Ig-opsonized target cells mature at a slower rate. The early maturation was shown to depend on activation of Rho acting through Rho kinase on ezrin-radixin-moesin proteins. Blockade of Rho signaling or inhibition of moesin both delayed maturation rates to those seen with opsonized targets. By contrast, phagosome maturation in dendritic cells was slower, similar between apoptotic and opsonized target cells, and unaffected by Rho inhibition. These observations have direct implications for the clearance of dying cells and the roles played by different phagocytes in antigen digestion and presentation.
Erwig
Lars-Peter
LP
Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. mmd288@abdn.ac.uk
McPhilips
Kathleen A
KA
Wynes
Murray W
MW
Ivetic
Alexander
A
Ridley
Anne J
AJ
Henson
Peter M
PM
D000143:Acids; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D000099149:Ezrin
D000143:Acids; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D020741:rho GTP-Binding Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin