Phosphatidylinositol-3' kinase-dependent vesicle formation in macrophages in response to macrophage colony stimulating factor.
Treatment of the BAC1.2F5 macrophage cell line with Macrophage Colony Stimulating Factor (M-CSF) resulted in a rapid induction of vesiculation that was reminiscent of macropinocytosis. Time-lapse micrography showed that these vesicles initiated as small vesicles at the cell periphery, but grew in size and migrated with time to a perinuclear localisation after growth factor stimulation. Immunofluorescence showed that the M-CSF receptor (c-fms) associated with the small vesicles and also the larger phase-bright vesicles. Treatment with two distinct inhibitors showed that the rapid initiation of vesicle formation was not dependent on phosphatidylinositol-3' (PI-3) kinase activity; however, the subsequent maintenance, maturation and translocation of the large, phase-bright, c-fms-containing vesicles was dependent on PI-3 kinase activity. The inhibitors could also reverse the further maturation of preformed vesicles. The inhibition of vesicle trafficking and maturation correlated with ablation of M-CSF-induced PI-3 kinase activity associated with p110(alpha). These data demonstrate a role for PI-3 kinase in vesicle trafficking and maintenance. PI-3 kinase activity was also necessary for the macropinocytotic response in macrophages, a process that is essential for efficient antigen processing and presentation in macrophage-like cells.
Murray
J
J
Yamanouchi Research Institute, Littlemore Park, Oxford OX4 4XS, UK.
Wilson
L
L
Kellie
S
S
D000818:Animals; D002460:Cell Line; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010873:Pinocytosis / Q000187:drug effects / Q000502:physiology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells
D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor