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limiting infection and modulating immune activation of alveolar macrophages.
3. Lung Pathophysiology: Characterization and analysis of alveolar injury and therapeutic strategies
in animal models of: a) Acute lung injury. b) Gram-negative bacterial infection, c) Allergic airway
inflammation. d)Lung transplant and ischemia-reperfusion injury.
4. Drug and biomolecule encapsulation for inhalatory administration:
a) Encapsulation of drug/biomolecules in nanoliposomes. b) Studies of amphipathic drug/membrane interaction. c) Nanoparticle stability evaluation. d) Characterization of the interaction of surfactant components with nanoparticles.
This research has direct relevance for the development of new therapies for inflammatory and infectious lung diseases.
Most relevant scientific articles
• Ruge C.A., Hillaireau H., Grabowski N., Beck-Broichsitter M., Canadas O., Tsapis N. et al. Pulmonary Surfactant Protein A-Mediated Enrichment of Surface-Decorated Polymeric Nanoparticles in Alveolar Macrophages. Molecular Pharmaceutics. 2016;13(12):4168-4178.
• Minutti C.M., Garca-Fojeda B., Saenz A., De Las Casas-Engel M., Guillamat-Prats R., De Lorenzo A. et al. Surfactant protein a prevents IFN-γ/IFN-γ receptor interaction and attenuates classical activation of human alveolar macrophages. Journal of Immunology. 2016;197(2):590-598.
Highlights
• Relevant research project: SAF2015-65307-R (2016-2018). Natural anti-infective factors of the lung as new therapeutic strategies against respiratory infections. Funded by the Spanish Ministry of Economy and Competitiveness. Principal Investigator: Cristina Casals.
RELEVANT RESULTS:
• Line 2: (i) SP-A inhibits [IFN-g+LPS]-induced classical activation of macrophages; (ii) binding of SP-A to IFN-g abrogates IFN-g effects on human macrophages; and (iii) SP-A amplifies IL-4-induced macrophage proliferation and alternative activation, revealing an important role of SP-A in respiratory diseases with high levels of IL-4, such as asthma or fibrosis. Additionally, (iv) SP-A exhibits an antimicrobial synergic action with both endogenous and exogenous antimicrobial peptides against different Gram-negative bacteria; (v) the formation of SP-A/antimicrobial peptide complexes is required for such synergistic activity; and (vi) the complexes cross the cell wall and translocate to the periplasmic space, where they interact with the cytoplasmic membrane.
• Line 3: In an animal model of HDM-induced allergic airway inflammation SP-A/surfactant lipid ratio is increased. Since SP-A potentiates IL-4 action on macrophages, but lipids inhibit them, the elevated SP-A/ lipid ratio may increase IL-4 effects in the alveoli during allergic inflammation.
• Line 4: SP-A-coated mannosylated nanoparticles exhibit a greater internalization by alveolar macrophages than non-SP-A-coated nanoparticles. This suggests that this formulation could be useful as a vehicle of anti-tuberculosis drugs.
DOCTORAL THESIS:
19/12/2016. Carlos Muñoz Minutti. “Regulation of alveolar macrophage activation by the pulmonary surfactant protein SP-A”. Complutense University of Madrid. Doctoral Program: Biochemistry, Molecular Biology and Biomedicine (“Mention of Excellence” by the Ministry of Science and Education). Evaluation: Excellent “cum laude”. Director: Dr. Cristina Casals and Dr. Belén García-Fojeda.
INTERNATIONAL COLLABORATION:
research groups 49
1) Prof. Dr. Timothy Weaver, Cincinnati Children’s Hospital (Ohio, USA); 2) Prof. Dr. Judith E. Allen, University of Edinburgh (U.K.); 3) Prof. Dr. Henk P. Haagsman (Utrecht University, Netherlands); 4) Prof. Dr. Elias Fattal (University of Paris-Sud in Châtenay-Malabry, France).
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