Person:
García-Fojeda García-Valdecasas, María Belén

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First Name
María Belén
Last Name
García-Fojeda García-Valdecasas
URI
https://hdl.handle.net/20.500.14352/76061
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2016 - 20172
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Author: Minutti, Carlos × Subject: 612.017 ×

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    Surfactant Protein A Prevents IFN-γ/IFN-γ Receptor Interaction and Attenuates Classical Activation of Human Alveolar Macrophages
    (Journal of Immunology, 2016) 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.
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    Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver
    (Science, 2017) Minutti, Carlos; Jackson-Jones, Lucy; García-Fojeda García-Valdecasas, María Belén; Knipper, Johanna ; Sutherland, Tara; Logan, Nicola; Ringqvist, Emma; Guillamat-Prats, Raquel; Ferenbach, David; Artigas, Antonio; Stamme, Cordula ; Chroneos, Zissis ; Zaiss, Dietmar ; Casals Carro, María Cristina; Allen, Judith
    The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of type 2-mediated macrophage activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL-4)-dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth. In the peritoneal cavity and liver, C1q enhancement of type 2 macrophage activation was required for liver repair after bacterial infection, but resulted in fibrosis after peritoneal dialysis. IL-4 drives production of these structurally related defense collagens, SP-A and C1q, and the expression of their receptor, myosin 18A. These findings reveal the existence within different tissues of an amplification system needed for local type 2 responses.