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Surfactant Protein A Prevents IFN-γ/IFN-γ Receptor Interaction and Attenuates Classical Activation of Human Alveolar Macrophages Minutti, Carlos García-Fojeda García-Valdecasas, María Belén Sáenz, Alejandra Casas-Engel, Mateo de las Guillamat-Prats, Raquel Lorenzo, Alba de Serrano-Mollar, Anna Corbí, Ängel Casals Carro, María Cristina Lung surfactant protein A (SP-A) plays an important function in modulating inflammation in the lung. However, the exact role of SP-A and the mechanism by which SP-A affects IFN-γ–induced activation of alveolar macrophages (aMϕs) remains unknown. To address these questions, we studied the effect of human SP-A on rat and human aMϕs stimulated with IFN-γ, LPS, and combinations thereof and measured the induction of proinflammatory mediators as well as SP-A’s ability to bind to IFN-γ or IFN-γR1. We found that SP-A inhibited (IFN-γ + LPS)–induced TNF-α, iNOS, and CXCL10 production by rat aMϕs. When rat macrophages were stimulated with LPS and IFN-γ separately, SP-A inhibited both LPS-induced signaling and IFN-γ–elicited STAT1 phosphorylation. SP-A also decreased TNF-α and CXCL10 secretion by ex vivo–cultured human aMϕs and M-CSF–derived macrophages stimulated by either LPS or IFN-γ or both. Hence, SP-A inhibited upregulation of IFN-γ–inducible genes (CXCL10, RARRES3, and ETV7) as well as STAT1 phosphorylation in human M-CSF–derived macrophages. In addition, we found that SP-A bound to human IFN-γ (KD = 11 ± 0.5 nM) in a Ca2+-dependent manner and prevented IFN-γ interaction with IFN-γR1 on human aMϕs. We conclude that SP-A inhibition of (IFN-γ + LPS) stimulation is due to SP-A attenuation of both inflammatory agents and that the binding of SP-A to IFN-γ abrogates IFN-γ effects on human macrophages, suppressing their classical activation and subsequent inflammatory response. 2024-01-22T17:24:10Z 2024-01-22T17:24:10Z 2016 journal article Carlos M. Minutti, Belén García-Fojeda, Alejandra Sáenz, Mateo de las Casas-Engel, Raquel Guillamat-Prats, Alba de Lorenzo, Anna Serrano-Mollar, Ángel L. Corbí, Cristina Casals; Surfactant Protein A Prevents IFN-γ/IFN-γ Receptor Interaction and Attenuates Classical Activation of Human Alveolar Macrophages. J Immunol 15 July 2016; 197 (2): 590–598. https://doi.org/10.4049/jimmunol.1501032 0022-1767 10.4049/jimmunol.1501032 https://hdl.handle.net/20.500.14352/94514 1550-6606 https://doi.org/10.4049/jimmunol.1501032 https://pubmed.ncbi.nlm.nih.gov/27271568/ eng info:eu-repo/grantAgreement/MINECO//SAF2012-32728/ES/EL SURFACTANTE PULMONAR COMO AGENTE PROTECTOR Y MODULADOR DE LA INFLAMACION E INFECCION EN EL PULMON/ info:eu-repo/grantAgreement/MINECO//SAF2015-65307-R/ES/FACTORES ANTI-INFECCIOSOS DEL PULMON COMO NUEVAS ESTRATEGIAS TERAPEUTICAS FRENTE A INFECCIONES RESPIRATORIAS/ info:eu-repo/grantAgreement/MINECO//SAF2014-52423-R/ES/MODULACION DE LA ACTIVACION DE MACROFAGOS Y DE PATOLOGIAS INFLAMATORIAS POR ACTIVINA A Y SEROTONINA/ FIS-PI13/00282 CIBERES-CB06/06/0002 MTV3 122410 AP2010-1524 http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International The American Association of Immunologists