Nitrogen mustard (melphalan) exposure of an in vitro coculture model in the human proximal respiratory system

Acute Morphological and Toxicological Effects in a Human Bronchial Coculture Model after Sulfur Mustard Exposure

International audience; Sulfur mustard (SM) is a strong alkylating agent. Inhalation of SM causes acute lung injury accompanied by severe disruption of the airway barrier. In our study, we tested the acute effects after mustard exposure in an in vitro coculture bronchial model of the proximal barrier. To achieve this, we seeded normal human bronchial epithelial explant-outgrowth cells (HBEC) together with lung fibroblasts as a bilayer on filter plates and exposed the bronchial model after 31 days of differentiation to various concentrations of SM (30, 100, 300, and 500mM). The HBEC formed confluent layers, expressing functional tight junctions as measured by transepithelial electrical resis…

Acute cytotoxicity and apoptotic effects after l-Pam exposure in different cocultures of the proximal and distal respiratory system.

Abstract Sulphur and nitrogen mustard are strong alkylating agents which can cause after inhalation acute lung injury in the larynx, trachea and large bronchi and can lead to alveolar edema. In our study we tested the N-Lost l -Phenylalanine Mustard ( l -Pam). Therefore we seeded the alveolar type II cell line NCI H441 on the upper membrane of a Transwell filter plate and the endothelial cell line ISO-Has-1 on the lower side of the membrane for the alveolar model and combined the human bronchial explant-outgrowth cells and fibroblasts in the bronchial model and exposed both models with various concentrations of l -Pam. Treatment with l -Pam led to a concentration-dependent decrease of the t…

Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood–air barrier

Cadmium (Cd{sup 2+}) is a widespread environmental pollutant, which is associated with a wide variety of cytotoxic and metabolic effects. Recent studies showed that intoxication with the heavy metal most importantly targets the integrity of the epithelial barrier. In our study, the lung epithelial cell line, NCI H441, was cultured with the endothelial cell line, ISO-HAS-1, as a bilayer on a 24-well HTS-Transwell (registered) filter plate. This coculture model was exposed to various concentrations of CdCl{sub 2}. The transepithelial electrical resistance decreased on the apical side only after treatment with high Cd{sup 2+} concentrations after 48 h. By contrast, a breakdown of TER to less t…

Investigation of different organophosphates in a human bronchial tripleculture model