Surfactant Protein A Prevents IFN-γ/IFN-γ Receptor Interaction and Attenuates Classical Activation of Human Alveolar Macrophages
| Autor: | Cristina Casals, Anna Serrano-Mollar, Angel L. Corbí, Mateo de las Casas-Engel, Raquel Guillamat-Prats, Alejandra Sáenz, Belén García-Fojeda, Carlos M. Minutti, Alba de Lorenzo |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Immunology Blotting Western Inflammation Real-Time Polymerase Chain Reaction Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences Interferon-gamma 0302 clinical medicine Downregulation and upregulation Internal medicine Macrophages Alveolar medicine Immunology and Allergy CXCL10 Animals Humans Secretion Receptor Receptors Interferon Pulmonary Surfactant-Associated Protein A Chemistry Macrophage Activation Surfactant protein A Cell biology Rats 030104 developmental biology Endocrinology Phosphorylation Cytokines medicine.symptom 030215 immunology |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1550-6606 |
| Popis: | 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 (aMfs) remains unknown. To address these questions, we studied the effect of human SP-A on rat and human aMfs 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-a, iNOS, and CXCL10 production by rat aMfs. 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-a and CXCL10 secretion by ex vivo-cultured human aMfs 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 6 0.5 nM) in a Ca2+-dependent manner and prevented IFN-γ interaction with IFN-γR1 on human aMfs. 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. |
| Databáze: | OpenAIRE |
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