{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:50:32Z","timestamp":1791341432106,"version":"4.3.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The anionic antimicrobial peptide SP-BN, derived from the N-terminal saposin-like domain of the surfactant protein (SP)-B proprotein, and SP-A are lung anti-infective proteins. SP-A\u2013deficient mice are more susceptible than wild-type mice to lung infections, and bacterial killing is enhanced in transgenic mice overexpressing SP-BN. Despite their potential anti-infective action, in vitro studies indicate that several microorganisms are resistant to SP-A and SP-BN. In this study, we test the hypothesis that these proteins act synergistically or cooperatively to strengthen each other\u2019s microbicidal activity. The results indicate that the proteins acted synergistically in vitro against SP-A\u2013 and SP-BN\u2013resistant capsulated Klebsiella pneumoniae (serotype K2) at neutral pH. SP-A and SP-BN were able to interact in solution (Kd = 0.4 \u03bcM), which enabled their binding to bacteria with which SP-A or SP-BN alone could not interact. In vivo, we found that treatment of K. pneumoniae\u2013infected mice with SP-A and SP-BN conferred more protection against K. pneumoniae infection than each protein individually. SP-A\/SP-BN\u2013treated infected mice showed significant reduction of bacterial burden, enhanced neutrophil recruitment, and ameliorated lung histopathology with respect to untreated infected mice. In addition, the concentrations of inflammatory mediators in lung homogenates increased early in infection in contrast with the weak inflammatory response of untreated K. pneumoniae\u2013infected mice. Finally, we found that therapeutic treatment with SP-A and SP-BN 6 or 24 h after bacterial challenge conferred significant protection against K. pneumoniae infection. These studies show novel anti-infective pathways that could drive development of new strategies against pulmonary infections.<\/jats:p>","DOI":"10.4049\/jimmunol.1500778","type":"journal-article","created":{"date-parts":[[2015,7,11]],"date-time":"2015-07-11T02:16:18Z","timestamp":1436580978000},"page":"1628-1636","source":"Crossref","is-referenced-by-count":35,"title":["Natural Anti-Infective Pulmonary Proteins: In Vivo Cooperative Action of Surfactant Protein SP-A and the Lung Antimicrobial Peptide SP-BN"],"prefix":"10.1093","volume":"195","author":[{"given":"Juan Manuel","family":"Coya","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Complutense University of Madrid , 28040 Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry T","family":"Akinbi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati College of Medicine , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"S\u00e1enz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Complutense University of Madrid , 28040 Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati College of Medicine , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E","family":"Weaver","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati College of Medicine , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Casals","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, Complutense University of Madrid , 28040 Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,15]]},"reference":[{"key":"2025030704030883200_r1","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/cc6820","article-title":"Gram-negative antibiotic resistance: there is a price to pay","volume":"12","author":"Slama","year":"2008","journal-title":"Crit. 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