Minutti, CarlosGarcía-Fojeda García-Valdecasas, María BelénSáenz, AlejandraCasas-Engel, Mateo de lasGuillamat-Prats, RaquelLorenzo, Alba deSerrano-Mollar, AnnaCorbí, ÄngelCasals Carro, María Cristina2024-01-222024-01-222016Carlos 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.15010320022-176710.4049/jimmunol.1501032https://hdl.handle.net/20.500.14352/94514Lung 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationaljournal article1550-6606https://doi.org/10.4049/jimmunol.1501032https://pubmed.ncbi.nlm.nih.gov/27271568/open access577.1612.017Surfactant protein AIFN-gammaAlveolar macrophages (AM)InflammationIFN-gamma receptorType 1 inflammationBioquímica (Biología)2403 Bioquímica