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Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>spores, kill vegetative<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>cells, and inactivate anthrax lethal factor. We now report that retrocyclins are extensively bound by components of native mouse, human, and fetal calf sera, that heat-inactivated sera show greatly enhanced retrocyclin binding, and that native and (especially) heat-inactivated sera greatly reduce the direct activities of retrocyclins against spores and vegetative cells of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>. Nevertheless, we also found that retrocyclins protected mice challenged<jats:italic>in vivo<\/jats:italic>by subcutaneous, intraperitoneal, or intranasal instillation of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>spores. Retrocyclin 1 bound extensively to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>spores and enhanced their phagocytosis and killing by murine RAW264.7 cells. Based on the assumption that spore-bound RC1 enters phagosomes by \u201cpiggyback phagocytosis,\u201d model calculations showed that the intraphagosomal concentration of RC1 would greatly exceed its extracellular concentration. Murine alveolar macrophages took up fluorescently labeled retrocyclin, suggesting that macrophages may also acquire extracellular RC1 directly. Overall, these data demonstrate that retrocyclins are effective<jats:italic>in vivo<\/jats:italic>against experimental murine anthrax infections and suggest that enhanced macrophage function contributes to this property.<\/jats:p>","DOI":"10.1128\/aac.00267-11","type":"journal-article","created":{"date-parts":[[2011,7,19]],"date-time":"2011-07-19T04:42:33Z","timestamp":1311050553000},"page":"4238-4250","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Humanized \u03b8-Defensins (Retrocyclins) Enhance Macrophage Performance and Protect Mice from Experimental Anthrax Infections"],"prefix":"10.1128","volume":"55","author":[{"given":"S.","family":"Welkos","sequence":"first","affiliation":[{"name":"Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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