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• W1980706507 startingPage "577" @default.
• W1980706507 abstract "The etiologic agent of inhalational anthrax, <i>Bacillus anthracis</i>, produces virulence toxins that are important in the disease pathogenesis. Current studies suggest that mouse and human macrophages are susceptible to immunosuppressive effects of one of the virulence toxins, lethal toxin (LT). Thus a paradigm has emerged that holds that the alveolar macrophage (AM) does not play a significant role in the innate immune response to <i>B. anthracis</i> or defend against the pathogen as it is disabled by LT. This is inconsistent with animal models and autopsy studies that show minimal disease at the alveolar surface. We examined whether AM are immunosuppressed by LT. We found that human AM were relatively resistant to LT-mediated innate immune cytokine suppression, MEK cleavage, and induction of apoptosis as compared with mouse RAW 264.7 macrophages. Mouse AM and murine bone marrow-derived macrophages were also relatively resistant to LT-mediated apoptosis despite intermediate sensitivity to MEK cleavage. The binding component of LT, protective Ag, does not attach to human AM, although it did bind to mouse AM, murine bone marrow-derived macrophages, and RAW 264.7 macrophages. Human AM do not produce significant amounts of the protective Ag receptor anthrax toxin receptor 1 (TEM8/ANTXR1) and anthrax toxin receptor 2 (CMG2/ANTXR2). Thus, mature and differentiated AM are relatively resistant to the effects of LT as compared with mouse RAW 264.7 macrophages. AM resistance to LT may enhance clearance of the pathogen from the alveolar surface and explain why this surface is relatively free of <i>B. anthracis</i> in animal models and autopsy studies." @default.
• W1980706507 created "2016-06-24" @default.
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• W1980706507 date "1988-09-01" @default.
• W1980706507 modified "2023-09-27" @default.
• W1980706507 title "Considerations in using linkage analysis as a presymptomatic test for Huntington's disease." @default.
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• W1980706507 doi "https://doi.org/10.1136/jmg.25.9.577" @default.
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