Transmembrane signaling: an ion-flux-independent model for signal transduction by complexed Fc receptors.
Fluxes of Na+/K+ that precede effector functions in stimulated phagocytes are thought to play a role in signal transduction. To examine this hypothesis, phagocytosis, phagosomal acidification, and superoxide anion generation (O2-) were stimulated in media in which the Na+ was replaced with K+ or choline+. Counts of particles internalized and assessment of acidification of the phagosomes by acridine orange staining indicated that Na+/K+ fluxes were not necessary for phagocytosis or phagosomal acidification in J774.2 macrophages. Phagocytosis mediated by the ionophoretic Fc receptor gamma 2b/gamma 1 of J774.2 macrophages was equally independent of a Na+ gradient. Na+/K+ fluxes did not dictate the rate of O2- generation in human monocytes. Therefore, in at least these three effector functions, Na+/K+ fluxes stimulated by Fc- and non-specific receptor binding play neither a signaling nor an enhancing role. An ion-flux-independent model for transmembrane signaling by the Fc receptor is proposed. Others have shown that there is an apparent dependence on the external Na+ concentration for O2- generation and lysosomal secretion by neutrophils. These neutrophils had been pre-treated with NH4+ during a routine purification step. O2- generation stimulated by opsonized zymosan or phorbol myristate acetate, by monocytes or monocyte-derived macrophages, and phagocytosis of opsonized zymosan by J774.2 macrophages, showed dependence on external Na+ only if these cells had been pre-treated with NH4+. Brief NH4+ pre-treatment would be expected to acidify the cytoplasm of the cells. The reversal of this acidification is known to require Na+ for H+ extrusion through the Na+/H+ antiport, thus explaining the apparent Na+ dependence.
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009580:Nitroblue Tetrazolium; D010101:Oxygen Consumption; D010587:Phagocytosis; D011961:Receptors, Fc / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D014617:Vacuoles / Q000648:ultrastructure
D003574:Cytochrome c Group; D011961:Receptors, Fc; D000643:Ammonium Chloride; D013481:Superoxides; D009580:Nitroblue Tetrazolium