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

Paper ID Volume ID Publish Year Pages File Format Full-Text
24362 43509 2010 7 PDF Available
Title
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 transepithelial electrical resistance and therefore impairment of barrier function in both models. Changes in morphology could be observed. In the bronchial model damaged cell organelles whereas in the alveolar model a widening of intercellular spaces could be seen. Loss of cell–matrix adhesion as well as apoptotic and necrotic cell death could be demonstrated.In conclusion, treatment with the nitrogen mustard in the coculture models showed comparable results to sulphur mustard treatment and thus this model could be useful to explore similarities and differences in signal transduction pathways after treatment with both sulphur and nitrogen mustard.

Keywords
HBEC, human bronchial epithelial explant-outgrowth cells; HBEC/Wi-38, coculture of HBEC with Wi-38; Iso-Has-1, endothelial cell line; l-Pam, Melphalan, Alkeran, 4-[bis-(chloroethyl)amino]phenylalanine; NCI H441, alveolar type II cell line; N-LostNM, nitro
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Acute cytotoxicity and apoptotic effects after l-Pam exposure in different cocultures of the proximal and distal respiratory system
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 148, Issue 1, 1 July 2010, Pages 31–37
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us