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
Search Results
Now showing 1 - 5 of 5
Item Role of lipid ordered/disordered phase coexistence in pulmonary surfactant function(Biochimica et Biophysica Acta (BBA) - Biomembranes, 2012) Casals Carro, María Cristina; Cañadas Benito, OlgaThe respiratory epithelium has evolved to produce a complicated network of extracellular membranes that are essential for breathing and, ultimately, survival. Surfactant membranes form a stable monolayer at the air-liquid interface with bilayer structures attached to it. By reducing the surface tension at the air-liquid interface, surfactant stabilizes the lung against collapse and facilitates inflation. The special composition of surfactant membranes results in the coexistence of two distinct micrometer-sized ordered/disordered phases maintained up to physiological temperatures. Phase coexistence might facilitate monolayer folding to form three-dimensional structures during exhalation and hence allow the film to attain minimal surface tension. These folded structures may act as a membrane reserve and attenuate the increase in membrane tension during inspiration. The present review summarizes what is known of ordered/disordered lipid phase coexistence in lung surfactant, paying attention to the possible role played by domain boundaries in the monolayer-to-multilayer transition, and the correlations of biophysical inactivation of pulmonary surfactant with alterations in phase coexistence.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 Bacterial lipopolysaccharide promotes destabilization of lung surfactant-like films(Biophysical Journal, 2011) Cañadas Benito, Olga; Keough, Kevin M.W.; Casals Carro, María CristinaThe airspaces are lined with a dipalmitoylphosphatidylcholine (DPPC)-rich film called pulmonary surfactant, which is named for its ability to maintain normal respiratory mechanics by reducing surface tension at the air-liquid interface. Inhaled airborne particles containing bacterial lipopolysaccharide (LPS) may incorporate into the surfactant monolayer. In this study, we evaluated the effect of smooth LPS (S-LPS), containing the entire core oligosaccharide region and the O-antigen, on the biophysical properties of lung surfactant-like films composed of either DPPC or DPPC/palmitoyloleoylphosphatidylglycerol (POPG)/palmitic acid (PA) (28:9:5.6, w/w/w). Our results show that low amounts of S-LPS fluidized DPPC monolayers, as demonstrated by fluorescence microscopy and changes in the compressibility modulus. This promoted early collapse and prevented the attainment of high surface pressures. These destabilizing effects could not be relieved by repeated compression-expansion cycles. Similar effects were observed with surfactant-like films composed of DPPC/POPG/PA. On the other hand, the interaction of SP-A, a surfactant membrane-associated alveolar protein that also binds to LPS, with surfactant-like films containing S-LPS increased monolayer destabilization due to the extraction of lipid molecules from the monolayer, leading to the dissolution of monolayer material in the aqueous subphase. This suggests that SP-A may act as an LPS scavenger.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 Uptake of nanoparticles by alveolar macrophages is triggered by surfactant protein A(Nanomedicine: Nanotechnology, Biology and Medicine, 2011) Ruge, Christian Arnold; Kirch, Julian; Cañadas Benito, Olga; Schneider, Marc; Pérez Gil, Jesús; Schaefer, Ulrich Friedrich; Casals Carro, María Cristina; Lehr, Claus MichaelUnderstanding the bio-nano interactions in the lungs upon the inhalation of nanoparticles is a major challenge in both pulmonary nanomedicine and nanotoxicology. To investigate the effect of pulmonary surfactant protein A (SP-A) on the interaction between nanoparticles and alveolar macrophages, we used magnetite nanoparticles (110-180 nm in diameter) coated with different polymers (starch, carboxymethyldextran, chitosan, poly-maleic-oleic acid, phosphatidylcholine). Cellular binding and uptake of nanoparticles by alveolar macrophages was increased for nanoparticles treated with SP-A, whereas albumin, the prevailing protein in plasma, led to a significant decrease. A significantly different adsorption pattern of SP-A, compared to albumin was found for these five different nanomaterials. This study provides evidence that after inhalation of nanoparticles, a different protein coating and thus different biological behavior may result compared to direct administration to the bloodstream