Person: Cañadas Benito, Olga
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First Name
Olga
Last Name
Cañadas Benito
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
5 results
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Now showing 1 - 5 of 5
Item Conserved bacterial-binding peptides of the scavenger-like human lymphocyte receptor CD6 protect from mouse experimental sepsis(Frontiers in Immunology, 2018) Martínez Florensa, Mario; Català, Cristina; Velasco de Andrés, María; Cañadas Benito, Olga; Fraile Ágreda, Víctor; Casadó Llombart, Sergi; Armiger Borràs, Noelia; Consuegra Fernández, Marta; Casals Carro, María Cristina; Lozano, Francisco; Kishore, UdaySepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM) and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.Item Lipid–protein and protein–protein interactions in the pulmonary surfactant system and their role in lung homeostasis(International Journal of Molecular Sciences, 2020) Cañadas Benito, Olga; Olmeda Lozano, Bárbara; Alonso Eugenio, Alejandro; Pérez-Gil, JesúsPulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface.Item Pulmonary surfactant protein A-mediated enrichment of surface-decorated polymeric nanoparticles in alveolar macrophages(Molecular Pharmaceutics, 2016) Ruge, Christian A.; Hillaireau, Hervé; Grabowski, Nadège; Beck-Broichsitter, Mortiz; Cañadas Benito, Olga; Tsapis, Nicolas; Casals Carro, María Cristina; Nicolas, Julien; Fattal, EliasSurfactant protein A (SP-A), a lung anti-infective protein, is a lectin with affinity for sugars found on fungal and micrococcal surfaces such as mannose. We synthesized a mannosylated poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) copolymer and used it to produce nanoparticles with a polyester (PLGA/PLA) core and a PEG shell decorated with mannose residues, designed to be strongly associated with SP-A for an increased uptake by alveolar macrophages. Nanoparticles made of the copolymers were obtained by nanoprecipitation and displayed a size of around 140 nm. The presence of mannose on the surface was demonstrated by zeta potential changes according to pH and by a strong aggregation in the presence of concanavalin A. Mannosylated nanoparticles bound to SP-A as demonstrated by dynamic light scattering and transmission electron microscopy. The association with SP-A increased nanoparticle uptake by THP-1 macrophages in vitro. In vivo experiments demonstrated that after intratracheal administration of nanoparticles with or without SP-A, SP-A-coated mannosylated nanoparticles were internalized by alveolar macrophages in greater proportion than SP-A-coated nonmannosylated nanoparticles. The data demonstrate for the first time that the pool of nanoparticles available to lung cells can be changed after surface modification, using a biomimetic approach.Item Polyhydroxyalkanoate nanoparticles for pulmonary drug delivery: interaction with lung surfactant(Nanomaterials, 2021) Cañadas Benito, Olga; García-García, Andrea; Prieto, M. Auxiliadora; Pérez-Gil, JesúsPolyhydroxyalkanoates (PHA) are polyesters produced intracellularly by many bacterial species as energy storage materials, which are used in biomedical applications, including drug delivery systems, due to their biocompatibility and biodegradability. In this study, we evaluated the potential application of this nanomaterial as a basis of inhaled drug delivery systems. To that end, we assessed the possible interaction between PHA nanoparticles (NPs) and pulmonary surfactant using dynamic light scattering, Langmuir balances, and epifluorescence microscopy. Our results demonstrate that NPs deposited onto preformed monolayers of DPPC or DPPC/POPG bind these surfactant lipids. This interaction facilitated the translocation of the nanomaterial towards the aqueous subphase, with the subsequent loss of lipid from the interface. NPs that remained at the interface associated with liquid expanded (LE)/tilted condensed (TC) phase boundaries, decreasing the size of condensed domains and promoting the intermixing of TC and LE phases at submicroscopic scale. This provided the stability necessary for attaining high surface pressures upon compression, countering the destabilization induced by lipid loss. These effects were observed only for high NP loads, suggesting a limit for the use of these NPs in pulmonary drug delivery.Item Synergistic action of antimicrobial lung proteins against Klebsiella pneumoniae(International Journal of Molecular Sciences, 2021) Fraile Ágreda, Víctor; Cañadas Benito, Olga; Weaver, Timothy E.; Casals Carro, CristinaAs key components of innate immunity, lung antimicrobial proteins play a critical role in warding off invading respiratory pathogens. Lung surfactant protein A (SP-A) exerts synergistic antimicrobial activity with the N-terminal segment of the SP-B proprotein (SP-BN) against Klebsiella pneumoniae K2 in vivo. However, the factors that govern SP-A/SP-BN antimicrobial activity are still unclear. The aim of this study was to identify the mechanisms by which SP-A and SP-BN act synergistically against K. pneumoniae, which is resistant to either protein alone. The effect of these proteins on K. pneumoniae was studied by membrane permeabilization and depolarization assays and transmission electron microscopy. Their effects on model membranes of the outer and inner bacterial membranes were analyzed by differential scanning calorimetry and membrane leakage assays. Our results indicate that the SP-A/SP-BN complex alters the ultrastructure of K. pneumoniae by binding to lipopolysaccharide molecules present in the outer membrane, forming packing defects in the membrane that may favor the translocation of both proteins to the periplasmic space. The SP-A/SP-BN complex depolarized and permeabilized the inner membrane, perhaps through the induction of toroidal pores. We conclude that the synergistic antimicrobial activity of SP-A/SP-BN is based on the capability of this complex, but not either protein alone, to alter the integrity of bacterial membranes.