{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T04:41:32Z","timestamp":1769661692775,"version":"3.49.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The etiologic agent of inhalational anthrax, Bacillus anthracis, 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 B. anthracis 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 B. anthracis in animal models and autopsy studies.<\/jats:p>","DOI":"10.4049\/jimmunol.0803406","type":"journal-article","created":{"date-parts":[[2009,10,7]],"date-time":"2009-10-07T20:54:54Z","timestamp":1254948894000},"page":"5799-5806","source":"Crossref","is-referenced-by-count":17,"title":["Resistance of Human Alveolar Macrophages to\n                    <i>Bacillus anthracis<\/i>\n                    Lethal Toxin"],"prefix":"10.1093","volume":"183","author":[{"given":"Wenxin","family":"Wu","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harshini","family":"Mehta","sequence":"additional","affiliation":[{"name":"Program in Immunology and Cancer, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaushik","family":"Chakrabarty","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Leland","family":"Booth","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth S","family":"Duggan","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krupa B","family":"Patel","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy D","family":"Ballard","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K Mark","family":"Coggeshall","sequence":"additional","affiliation":[{"name":"Program in Immunology and Cancer, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan P","family":"Metcalf","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"},{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,11,1]]},"reference":[{"key":"2026012811151646500_R1","first-page":"815","article-title":"Anthrax.","volume-title":"N. Engl. J. Med.","year":"1999"},{"key":"2026012811151646500_R2","first-page":"1202","article-title":"The Sverdlovsk anthrax outbreak of 1979.","volume-title":"Science","year":"1994"},{"key":"2026012811151646500_R3","first-page":"359","article-title":"Studies on respiratory infection. I. The influence of particle size on respiratory infection with anthrax spores.","volume-title":"J. Hyg.","year":"1953"},{"key":"2026012811151646500_R4","first-page":"1055","article-title":"Experimental inhalation anthrax in the chimpanzee.","volume-title":"Am. J. Pathol.","year":"1959"},{"key":"2026012811151646500_R5","first-page":"7994","article-title":"Lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary route.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012811151646500_R6","first-page":"482","article-title":"Quantitative pathology of inhalational anthrax I: quantitative microscopic findings.","volume-title":"Mod. Pathol.","year":"2001"},{"key":"2026012811151646500_R7","first-page":"469","article-title":"Roles of macrophages and neutrophils in the early host response to Bacillus anthracis spores in a mouse model of infection.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012811151646500_R8","first-page":"405","article-title":"The alveolar macrophage: the Trojan horse of Bacillus anthracis.","volume-title":"Trends Microbiol.","year":"2002"},{"key":"2026012811151646500_R9","first-page":"485","article-title":"The pathogenesis of anthrax following the administration of spores by the respiratory route.","volume-title":"J. Pathol. Bacteriol.","year":"1957"},{"key":"2026012811151646500_R10","first-page":"795","article-title":"Differences in susceptibility of inbred mice to Bacillus anthracis.","volume-title":"Infect. Immun.","year":"1986"},{"key":"2026012811151646500_R11","first-page":"656","article-title":"The host response to anthrax lethal toxin: unexpected observations.","volume-title":"J. Clin. Invest.","year":"2003"},{"key":"2026012811151646500_R12","first-page":"10198","article-title":"On the role of macrophages in anthrax.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1993"},{"key":"2026012811151646500_R13","first-page":"6067","article-title":"Toxin-deficient mutants of Bacillus anthracis are lethal in a murine model for pulmonary anthrax.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012811151646500_R14","first-page":"129","article-title":"Studies on immunity in anthrax. VI. Immunizing activity of protective antigen against various strains of Bacillus anthracis.","volume-title":"J. Immunol.","year":"1955"},{"key":"2026012811151646500_R15","first-page":"3414","article-title":"Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model.","volume-title":"Infect. Immun.","year":"2007"},{"key":"2026012811151646500_R16","first-page":"394","article-title":"Immunological correlates for protection against intranasal challenge of Bacillus anthracis spores conferred by a protective antigen-based vaccine in rabbits.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012811151646500_R17","first-page":"2048","article-title":"Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition.","volume-title":"Science","year":"2002"},{"key":"2026012811151646500_R18","first-page":"1173","article-title":"Anthrax toxin receptor 2 mediates Bacillus anthracis killing of macrophages following spore challenge.","volume-title":"Cell Microbiol.","year":"2005"},{"key":"2026012811151646500_R19","first-page":"4430","article-title":"Bacillus anthracis spores stimulate cytokine and chemokine innate immune responses in human alveolar macrophages through multiple mitogen-activated protein kinase pathways.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012811151646500_R20","first-page":"193","article-title":"Quantitative measurement of anthrax toxin receptor messenger RNA in primary mononuclear phagocytes.","volume-title":"Microb. Pathog.","year":"2006"},{"key":"2026012811151646500_R21","first-page":"1175","article-title":"Macrophage-derived cell lines do not express proinflammatory cytokines after exposure to Bacillus anthracis lethal toxin.","volume-title":"Infect. Immun.","year":"2001"},{"key":"2026012811151646500_R22","first-page":"6142","article-title":"Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1991"},{"key":"2026012811151646500_R23","first-page":"9508","article-title":"Autophosphorylation in vitro of recombinant 42-kilodalton mitogen-activated protein kinase on tyrosine.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1991"},{"key":"2026012811151646500_R24","first-page":"289","article-title":"Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase.","volume-title":"J. Appl. Microbiol.","year":"1999"},{"key":"2026012811151646500_R25","first-page":"734","article-title":"Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor.","volume-title":"Science","year":"1998"},{"key":"2026012811151646500_R26","first-page":"349","article-title":"Lethal toxin of Bacillus anthracis causes apoptosis of macrophages.","volume-title":"Biochem. Biophys. Res. Commun.","year":"2002"},{"key":"2026012811151646500_R27","first-page":"224","article-title":"Cytotoxic effects of anthrax lethal toxin on macrophage-like cell line J774A.1.","volume-title":"Curr. Microbiol.","year":"1996"},{"key":"2026012811151646500_R28","first-page":"5029","article-title":"Anthrax lethal toxin impairs innate immune functions of alveolar macrophages and facilitates Bacillus anthracis survival.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012811151646500_R29","first-page":"1634","article-title":"Inactivation of Bacillus anthracis spores in murine primary macrophages.","volume-title":"Cell Microbiol.","year":"2006"},{"key":"2026012811151646500_R30","first-page":"5227","article-title":"Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization.","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2026012811151646500_R31","first-page":"5170","article-title":"Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2003"},{"key":"2026012811151646500_R32","first-page":"211","article-title":"Effect of Bacillus anthracis lethal toxin on human peripheral blood mononuclear cells.","volume-title":"FEBS Lett.","year":"2002"},{"key":"2026012811151646500_R33","first-page":"1291","article-title":"Exogenous \u03b3 and \u03b1\/\u03b2 interferon rescues human macrophages from cell death induced by Bacillus anthracis.","volume-title":"Infect. Immun.","year":"2004"},{"key":"2026012811151646500_R34","first-page":"41137","article-title":"Catalase plays a critical role in the CSF-independent survival of human macrophages via regulation of the expression of BCL-2 family.","volume-title":"J. Biol. Chem.","year":"2005"},{"key":"2026012811151646500_R35","first-page":"245","article-title":"De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells.","volume-title":"Cell Death Differ.","year":"1999"},{"key":"2026012811151646500_R36","first-page":"901","article-title":"IAP survivin regulates atherosclerotic macrophage survival.","volume-title":"Arterioscler. Thromb. Vasc. Biol.","year":"2007"},{"key":"2026012811151646500_R37","first-page":"6786","article-title":"In vivo protective role of human group IIa phospholipase A2 against experimental anthrax.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012811151646500_R38","first-page":"e187","article-title":"Edema toxin impairs anthracidal phospholipase A2 expression by alveolar macrophages.","volume-title":"PLoS Pathog.","year":"2007"},{"key":"2026012811151646500_R39","first-page":"5978","article-title":"Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax.","volume-title":"Infect. Immun.","year":"2005"},{"key":"2026012811151646500_R40","first-page":"5545","article-title":"Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012811151646500_R41","first-page":"329","article-title":"Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin.","volume-title":"Nature","year":"2003"},{"key":"2026012811151646500_R42","first-page":"86","article-title":"Resident CD11c+ lung cells are impaired by anthrax toxins after spore infection.","volume-title":"J. Infect. Dis.","year":"2006"},{"key":"2026012811151646500_R43","first-page":"24","article-title":"Bacillus anthracis aerosols in goat hair processing mills.","volume-title":"Am. J. Hyg.","year":"1960"},{"key":"2026012811151646500_R44","first-page":"83","article-title":"Inhalation anthrax.","volume-title":"Ann. NY Acad. Sci.","year":"1980"},{"key":"2026012811151646500_R45","first-page":"2236","article-title":"Anthrax as a biological weapon, 2002: updated recommendations for management.","volume-title":"J. Am. Med. 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