title: Interferon-gamma- and rickettsia-induced killing of macrophage-like cells is inhibited by anti-rickettsial antibodies and does not require the respiratory burst.
abstract: The effects of antibiotics and anti-rickettsial antibodies on the ability of Rickettsia prowazekii to kill interferon-gamma (IFN-gamma)-treated macrophage-like RAW264.7 cells and the possible involvement of the macrophage respiratory burst in this killing were investigated. Rifampicin and chloramphenicol, antibiotics that inhibited rickettsial growth, did not inhibit the ability of the rickettsiae to kill IFN-gamma-treated RAW264.7 cells. However, pretreatment of R. prowazekii with anti-rickettsial IgG (which inhibits rickettsial growth in macrophage-like cells) inhibited the killing. This anti-rickettsial IgG did not inhibit association of the rickettsiae with the cells. Although untreated and IFN-gamma-treated RAW264.7 cells underwent a respiratory burst when exposed to a stimulant such as opsonized zymosan or phorbol myristate acetate (PMA), infection of such cells with R. prowazekii was not associated with a measurable respiratory burst, as determined by monitoring hydrogen peroxide (H2O2) production and hexose monophosphate shunt activity. Furthermore, a variant macrophage-like cell line (J774.C3C) which lacks the ability to undergo a respiratory burst was killed by the combination of IFN-gamma treatment and R. prowazekii infection. These data define three interesting features of the killing of macrophage-like cells by IFN-gamma and R. prowazekii: (i) the macrophage respiratory burst is not required; (ii) anti-rickettsial antibiotics are not inhibitory; and (iii) anti-rickettsial antibodies are inhibitory.
authors.affiliation: Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile 36688.
authors.forename: J
authors.initials: J
authors.lastname: Turco
authors.forename: A
authors.initials: A
authors.lastname: Keysary
authors.forename: H H
authors.initials: HH
authors.lastname: Winkler
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000907:Antibodies, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D002701:Chloramphenicol / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010101:Oxygen Consumption / Q000187:drug effects; D011994:Recombinant Proteins; D012283:Rickettsia prowazekii / Q000187:drug effects / Q000276:immunology*; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D011994:Recombinant Proteins; D002701:Chloramphenicol; D007371:Interferon-gamma; D012293:Rifampin