title: Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS).
abstract: Occupational asthma can be induced by a number of chemicals at the workplace. Risk assessment of potential sensitizers is mostly performed in animal experiments. With increasing public demand for alternative methods, human precision-cut lung slices (PCLS) have been developed as an ex vivo model. Human PCLS were exposed to increasing concentrations of 20 industrial chemicals including 4 respiratory allergens, 11 contact allergens, and 5 non-sensitizing irritants. Local respiratory irritation was characterized and expressed as 75% (EC25) and 50% (EC50) cell viability with respect to controls. Dose-response curves of all chemicals except for phenol were generated. Local respiratory inflammation was quantified by measuring the production of cytokines and chemokines. TNF-α and IL-1α were increased significantly in human PCLS after exposure to the respiratory sensitizers trimellitic anhydride (TMA) and ammonium hexachloroplatinate (HClPt) at subtoxic concentrations, while contact sensitizers and non-sensitizing irritants failed to induce the release of these cytokines to the same extent. Interestingly, significant increases in T(H)1/T(H)2 cytokines could be detected only after exposure to HClPt at a subtoxic concentration. In conclusion, allergen-induced cytokines were observed but not considered as biomarkers for the differentiation between respiratory and contact sensitizers. Our preliminary results show an ex vivo model which might be used for prediction of chemical-induced toxicity, but is due to its complex three-dimensional structure not applicable for a simple screening of functional and behavior changes of certain cell populations such as dendritic cells and T-cells in response to allergens.
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Lauenstein
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Switalla
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Prenzler
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Seehase
authors.affiliation: KRH-Klinikum Nordstadt, Hanover, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Pfennig
authors.affiliation: KRH-Klinikum Nordstadt, Hanover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Förster
authors.affiliation: KRH-Klinikum Nordstadt, Hanover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Fieguth
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Braun
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, Germany. Electronic address: katherina.sewald@item.fraunhofer.de.
authors.forename: K
authors.initials: K
authors.lastname: Sewald
mesh_terms: D000368:Aged; D000485:Allergens / Q000276:immunology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D008168:Lung / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D046509:Tissue Culture Techniques
chemical_list: D000485:Allergens; D016207:Cytokines; D007509:Irritants
keywords: Asthma; Contact sensitizer; Low-molecular-weight chemicals; Pro-inflammatory cytokines; Respiratory allergy; Respiratory sensitizer