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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Multiphoton microscopy: an optical approach to understanding and resolving sulfur mustard lesions.

Sulfur mustard (SM; 2,2(')-dichloroethyl sulfide) is a percutaneous alkylating agent first used as a chemical weapon at Ypres, Belgium, in World War I. Despite its well-documented history, the primary lesions effecting dermal-epidermal separation and latent onset of incapacitating blisters remain poorly understood. By immunofluorescent imaging of human epidermal keratinocytes (HEK) and epidermal tissues exposed to SM (400 microM for 5 min), we have amassed unequivocal evidence that SM disrupts adhesion complex molecules, which are also disrupted by epidermolysis bullosa-type blistering diseases of the skin. Images of keratin 14 ( K14) in control cells showed tentlike filament networks linking the HEK's basolateral anchoring sites to the dorsal surface of its nuclei. Images from 6-h postexposure profiles revealed early disruption (</=1 h) and progressive collapse of the K14 cytoskeleton. Collapse involved focal erosions, loss of functional asymmetry, and displacement of nuclei beneath a mat of jumbled filaments. In complementary studies, 1-h images showed statistically significant (p<0.01) decreases of 25 to 30% in emissions from labeled alpha(6)beta(4) integrin and laminin 5, plus disruption of their receptor-ligand organization. Results indicate that SM alkylation destabilizes dermal-epidermal attachments and potentiates vesication by disrupting adhesion complex molecules and associated signaling mechanisms required for their maintenance and repair.[1]


  1. Multiphoton microscopy: an optical approach to understanding and resolving sulfur mustard lesions. Werrlein, R.J., Madren-Whalley, J.S. Journal of biomedical optics. (2003) [Pubmed]
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