title: Cytosolic free calcium is essential for immunoglobulin G-stimulated intracellular killing of Staphylococcus aureus by human monocytes.
abstract: Earlier studies have shown that the intracellular killing of Staphylococcus aureus by human monocytes requires continuous stimulation by serum factors, e.g., immunoglobulin G (IgG). In the present study, we demonstrate that IgG, at concentrations that stimulate the intracellular killing of S. aureus, induces a transient increase in the intracellular free calcium concentration ([Ca2+]i) in monocytes. The Ca2+ ionophores A23187 and ionomycin stimulate the killing process as efficiently as IgG does and initiate O2- production in resting monocytes but not in monocytes containing bacteria. The Ca2+ ionophore-stimulated killing process was markedly inhibited by the NADPH oxidase inhibitor diphenyleneiodonium bisulfate, which indicates that these ionophores stimulate oxygen-dependent bactericidal mechanisms. Reduction of the [Ca2+]i to values below 1 nM, obtained by loading monocytes with MAPT/AM (1,2-bis-5-methyl-aminophenoxylethane-N,N,N',N'-tetraacetoxymet hyl acetate) in the absence of extracellular Ca2+, rendered the cells unresponsive to IgG or Ca2+ ionophore stimulation of the intracellular killing of S. aureus, but the response could be restored by reincubating these cells in the presence of extracellular Ca2+. It is concluded that cytosolic free Ca2+ is essential for the IgG-stimulated intracellular killing of S. aureus by human monocytes.
authors.affiliation: Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: P H
authors.initials: PH
authors.lastname: Nibbering
authors.forename: R
authors.initials: R
authors.lastname: van Furth
mesh_terms: D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008274:Magnesium / Q000502:physiology; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000276:immunology; D013481:Superoxides / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D013481:Superoxides; D008274:Magnesium; D002118:Calcium