title: Alteration of macrophage responsiveness to platelet-activating factor by interferon-gamma and lipopolysaccharide.
abstract: Platelet-activating factor (PAF) can modulate several macrophage responses associated with tumoricidal and inflammatory activity. To determine how macrophage responsiveness to PAF may be altered by interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS), we studied PAF receptor-associated activities. Pretreatment of murine peritoneal macrophages with either LPS or IFN-gamma suppressed macrophage responsiveness to both PAF-induced calcium mobilization and superoxide anion (O2-) production. This suppression of macrophage responsiveness to PAF was maximal when 25 U/ml IFN-gamma or 100 ng/ml LPS was initially added for 6 hr. Macrophages pretreated with LPS or IFN-gamma remained refractory to PAF-induced rise in intracellular calcium for 4 to 24 hr. Macrophages preincubated with 25 U/ml IFN-gamma remained refractory to PAF-induced calcium mobilization for up to 4 hr. LPS and IFN-gamma treatment also decreased PAF-induced, calcium-dependent O2- production. When added together, IFN-gamma increased the suppression of PAF-induced intracellular calcium mobilization and inhibited O2- production mediated by LPS. To assess whether suppression was mediated through altered PAF receptors, binding affinities were determined; two binding affinities were demonstrated. Initial incubation of macrophages with LPS or IFN-gamma added alone or together decreased the number of cell surface PAF receptors and their binding affinity. These studies demonstrated that pretreatment with IFN-gamma and LPS can suppress select PAF-induced macrophage functions. Downregulation of PAF receptor activity may represent a means by which macrophages regulate the capacity and magnitude of some PAF-induced responses.
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis 95616-8643, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Howard
authors.forename: K L
authors.initials: KL
authors.lastname: Erickson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D013481:Superoxides; D007371:Interferon-gamma; D002118:Calcium