title: Phagocytosis of IgG-coated polystyrene beads by macrophages induces and requires high membrane order.
abstract: The biochemical composition and biophysical properties of cell membranes are hypothesized to affect cellular processes such as phagocytosis. Here, we examined the plasma membranes of murine macrophage cell lines during the early stages of uptake of immunoglobulin G (IgG)-coated polystyrene particles. We found that the plasma membrane undergoes rapid actin-independent condensation to form highly ordered phagosomal membranes, the biophysical hallmark of lipid rafts. Surprisingly, these membranes are depleted of cholesterol and enriched in sphingomyelin and ceramide. Inhibition of sphingomyelinase activity impairs membrane condensation, F-actin accumulation at phagocytic cups and particle uptake. Switching phagosomal membranes to a cholesterol-rich environment had no effect on membrane condensation and the rate of phagocytosis. In contrast, preventing membrane condensation with the oxysterol 7-ketocholesterol, even in the presence of ceramide, blocked F-actin dissociation from nascent phagosomes and particle uptake. In conclusion, our results suggest that ordered membranes function to co-ordinate F-actin remodelling and that the biophysical properties of phagosomal membranes are essential for phagocytosis.
authors: Centre for Vascular Research, University of New South Wales, Sydney, Australia.
authors: Astrid
authors: A
authors: Magenau
authors: Carola
authors: C
authors: Benzing
authors: Nicholas
authors: N
authors: Proschogo
authors: Anthony S
authors: AS
authors: Don
authors: Leila
authors: L
authors: Hejazi
authors: Denuja
authors: D
authors: Karunakaran
authors: Wendy
authors: W
authors: Jessup
authors: Katharina
authors: K
authors: Gaus
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D018699:Coated Vesicles / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D011137:Polystyrenes / Q000737:chemistry*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013261:Sterols / Q000378:metabolism
chemical_list: D000199:Actins; D002518:Ceramides; D007074:Immunoglobulin G; D008563:Membrane Lipids; D011137:Polystyrenes; D013109:Sphingomyelins; D013261:Sterols; D002784:Cholesterol; D013108:Sphingomyelin Phosphodiesterase