Imaging Sulfur Mustard Lesions in Basal Cells and Human Epidermal Tissues by Confocal and Multiphoton Laser Scanning Microscopy

Werrlein, Robert J.; Madren-Whalley, Janna S.

doi:10.1201/9780203008799.ch27

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…By 1 and 2 h after exposure, most HEK had lost their central polarized stress fibers, and were enveloped in an oval ring of basolateral actin filaments indicating a loss of polarized mobility. HEK continued to show lamellipodia and filopodia during that 2-h period; however, previous studies have indicated a concurrent loss of 6 4 and 3 1 integrins from these processes 1,2,16 . Displacement of the integrin receptors and disorganization of the actin cytoskeleton precludes the maintenance of their normal signaling pathways and associated repair mechanisms.…”

Section: Discussionmentioning

confidence: 86%

Multiphoton imaging the disruptive nature of sulfur mustard lesions

Werrlein¹,

Braue²,

Dillman³

2005

SPIE Proceedings

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Sulfur mustard [bis-2-chloroethyl sulfide] is a vesicating agent first used as a weapon of war in WWI. It causes debilitating blisters at the epidermal-dermal junction and involves molecules that are also disrupted by junctional epidermolysis bullosa (JEB) and other blistering skin diseases. Despite its recurring use in global conflicts, there is still no completely effective treatment. We have shown by imaging human keratinocytes in cell culture and in intact epidermal tissues that the basal cells of skin contain well-organized molecules (keratins K5/K14, 6 4 integrin, laminin 5 and 3 1 integrin) that are early targets of sulfur mustard. Disruption and collapse of these molecules is coincident with nuclear displacement, loss of functional asymmetry, and loss of polarized mobility. The progression of this pathology precedes basal cell detachment by 8-24 h, a time equivalent to the "clinical latent phase" that defines the extant period between agent exposure and vesication. Our images indicate that disruption of adhesion-complex molecules also impairs cytoskeletal proteins and the integration of structures required for signal transduction and tissue repair. We have recently developed an optical system to test this hypothesis, i.e., to determine whether and how the early disruption of target molecules alters signal transduction. This environmentally controlled on-line system provides a nexus for realtime correlation of imaged lesions with DNA microarray analysis, and for using multiphoton microscopy to facilitate development of more effective treatment strategies.

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Section: Discussionmentioning

confidence: 86%

Multiphoton imaging the disruptive nature of sulfur mustard lesions

Werrlein¹,

Braue²,

Dillman³

2005

SPIE Proceedings

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“…10͒ are well served by the topographic complexity of the ventral epidermis. In fact, images presented in previous multiphoton studies 16 showed the extent to which ␣ 6 ␤ 4 integrins occupy the elaborate surface area provided by rete pegs and ridges. While the elaborate matrix of integrin receptors enhances the adhesive strength of epidermal-dermal junctions, it is increasingly clear that ␣ 6 ␤ 4 integrins and laminin 5 provide basal cells with much more than simple attachment sites.…”

Section: Effects Of Sm On ␣ 6 ␤ 4 Integrin and Lamininmentioning

confidence: 94%

“…[13][14] However, EBS blisters occur above the hemidesmosomes 14 and not at the epidermal-dermal junction, as do SM blisters. 15,16 Accordingly, we have tried to determine whether the toxic effects of SM on keratin filaments also include associated proteins and ultimately the structural integrity of adhesion complex molecules. The rationale for that question lies in knowing that hemidesmosomes link transmembrane ␣ 6 ␤ 4 integrin receptors to keratin filaments 17 and to the basement membrane via plectin, 18 -21 bullous pemphigoid antigens, 14,22,23 and laminin 5.…”

Section: Introductionmentioning

confidence: 99%

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

Werrlein

Madren-Whalley

2003

J. Biomed. Opt.

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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 (

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Multiphoton imaging: a view to understanding sulfur mustard lesions

Werrlein¹,

Madren-Whalley²

2003

SPIE Proceedings

View full text Add to dashboard Cite

Imaging Sulfur Mustard Lesions in Basal Cells and Human Epidermal Tissues by Confocal and Multiphoton Laser Scanning Microscopy

Cited by 3 publications

References 15 publications

Multiphoton imaging the disruptive nature of sulfur mustard lesions

Multiphoton imaging the disruptive nature of sulfur mustard lesions

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

Multiphoton imaging: a view to understanding sulfur mustard lesions

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