Inhalation Toxicology: Local and systemic effects of inhaled particles.
Ernesto Alfaro-Moreno, PhD
Inhaled particles have been related to increases in deaths, visits to emergency rooms, and higher risk of diseases such as lung fibrosis, cancer, cardiovascular and neurological damages. In our group we are focused on the study of the mechanisms of cellular communication induced by particulate matter and the way these communications trigger adverse outcomes, in the lung and at distant organs. We use mainly in vitro models, with multiple cell co-cultures to mimic the in vivo response. One of our main aims is to understand the communication between the alveolar space and the vascular endothelium, and how this communication triggers the expression of proinflammatory molecules, the activation of monocytes, the recruitment of inflammatory cells, and the possible influence of these events on cancer. When necessary, we are also open to use studies using animal models, to validate our in vitro findings.
Bahare Kourangi Esfahani, Bachelor Student from the Stockholm University
Sofie Van Den Broucke, PhD student from the K.U. Leuven, Belgium
Raúl Omar Quintana-Belmares, PhD student from the National University of Mexico
Andrea Cediel Ulloa
Inhaled particulate matter effects on local and distant targets: Developing in vitro methods to assess cellular communication
Develop and characterize a multiple co-culture mimicking the alveoli, including lung epithelial cells, macrophages, mast cells and endothelial cells in an air-liquid interface (ALI) fashion.
Using multiple chambers connected with a flow of medium, develop and characterize a model that
mimics the systemic communication of different organs of the body.
Test the models with different types of particles (PM10, PM2.5, indoor dust and nanoparticles).
Analyze the physiological function of extracellular vesicles in communication between lung cells and their use as toxicity biomarkers.
Exposure to different components present in complex mixtures of urban particles: Prediction of exposure using in silico tools.
Using the concentrations of a wide variety of components present in urban particulate matter that we find in our studies characterization, we are using in silico models where physiological parameters of breathing are used to evaluate the possible levels of exposure to each component present in these complex mixtures.
Currently our team has ongoing collaborations with different groups and institutions in Sweden and around the world:
SWETOX (Annette Krais, Daniel Muncs)
IMM, Karolinska Institute, Sweden (Hanna Karlsson)
National Institute of Cancer of Mexico (Environmental Health Laboratory)
Institute of Geophysics (Ofelia Morton) and the Center of Atmospheric Sciences (Omar Amador and Irma Rosas) of the National University of Mexico
Pneumology Section of the K.U. Leuven, Belgium (Peter Hoet)
Institute of Physics of the Jagiellonian University at Krakow, Poland (Ewa Stepien)
Department of Toxicology of the Gazi University at Ankara, Turkey (Basak Engin).
Rueda-Romero C, Hernández-Pérez G, Ramos-Godínez P, Vázquez-López I, Quintana-Belmares RO, Huerta-García E, Stepien E, López-Marure R, Montiel-Dávalos A, Alfaro-Moreno E. Titanium dioxide nanoparticles induce the expression of early and late receptors for adhesion molecules on monocytes. Particle and Fibre Toxicology 2016; 13(36). DOI 10.1186/s12989-016-0147-3
Huerta-García E, Marquez-Ramirez SG, Ramos-Godinez MP, Lopez-Saavedra A, Herrera-Montalvo LA, Parra A, Alfaro-Moreno E, Gomez EO, López-Marure R. Internalization of titanium dioxide nanoparticles by glial cells is given at short times and is mainly mediated by actin reorganization-dependent endocytosis. NeuroToxicology 2015; 51:27-37 DOI:10.1016/j.neuro.2015.08.013
Quintana R, Alfaro-Moreno E, García-Cuellar CM, et al. Evaluation of the oxidative potential of urban PM and its relation to in vitro induced DNA damage: a spatial and temporal comparison. Revista Internacional de Contaminacion Ambiental 2015; 31(2): 145-154
Nemmar A, Holme J, Rosas I, Schwarze P, Alfaro-Moreno E. Recent advances in Particulate Matter and Nanoparticle toxicology: A review of the in vivo and in vitro studies. Biomed Res Int. 2013; ID 279371
Huerta-García E, Montiel-Davalos A, Alfaro-Moreno E, Gutierrez-Iglesias G, Lopez-Marure R. Dehydroepiandrosterone protects endothelial cells against inflammatory events induced by urban particulate matter and titanium dioxide nanoparticles. Biomed Res Int 2013; ID 382058, DOI: 10.1155/2013/382058
Ramos-Godínez P, González-Gómez BE, Montiel-Dávalos A, López-Marure R, Alfaro-Moreno E. TiO2 nanoparticles induce endothelial cell activation in a pneumocyte-endothelial co-culture model. Toxicology in Vitro 2013; 27: 774-781 DOI:10.1016/j.tiv.2012.12.010
Montiel-Dávalos A, Ventura-Gallegos JL, Alfaro-Moreno E, et al. TiO2 nanoparticles induce dysfunction and activation of human endothelial cells. Chem Res Toxicol 2012; 25(4): 920-930 DOI: 10.1021/tx200551u
Strength in complexity: Cytokine and chemokine release screening after exposure to titanium dioxide nanoparticles. Andrea Paola Cediel Ulloa, Master in Toxicology, Karolinska Institutet, Sweden. 2015-2016
Development of a co-culture model containing different types of cells at an air-liquid interface that mimics human lung alveoli for the toxicity testing of nanoparticles: Pitfalls, difficulties and concerns. Anneli Sara Banderby, Master in Toxicology, Karolinska Institutet, Sweden. 2015-2016
Master Students are welcome to participate in our projects.
Film clips or audio
Local and systemic effects induced by inhaled particles: What do we know so far?