Effects of sulfur mustard on the basal cell adhesion complex†

Autor: Robert J. Werrlein, Janna S. Madren-Whalley
Rok vydání: 2001
Předmět:
Zdroj: Journal of Applied Toxicology. 20:S115-S123
ISSN: 0260-437X
DOI: 10.1002/1099-1263(200012)20:1+<::aid-jat682>3.0.co;2-q
Popis: Among the most intriguing questions about sulfur mustard (di(2-chloroethyl) sulfide) is why basal cells are the primary targets of its vesicating lesions. To investigate this problem, replicate cultures of human epidermal keratinocytes (HEK) were grown from normal skin and exposed to 400 μM sulfur mustard (HD) for 5 min. Using fluorescein isothiocyanate (FITC)-conjugated antibodies, confocal laser microscopy and image analyses, we found that in early passages, sham-treated HEK maintained in a 0.15 mM Ca 2+ medium continued to express keratins K5 and K14 as well as α 6 β 4 -integrin. Both K5 and K14 are intermediate filaments characteristic of basal cells and linked with attachment mechanisms effecting epidermolysis bullosa simplex, a family of blistering skin diseases. Acute exposure to HD caused a statistically significant (P < 0.01) 30.74% decrease in K14 fluorescence within 1 h of exposure. Within 2 h of exposure, K14 fluorescence decreased to near-zero values. The loss in expression of K14 was progressive and occurred well before the expected appearance of in vivo blisters, which have a dose-dependent, clinical latent phase of 8-24 h. Acute exposure to HD also caused a statistically significant (P < 0.002) decrease in expression of β 4 , an integrin which has been associated with junctional epidermolysis bullosa (JEB). Disruption of K14 and α 6 β 4 -integrin may be early events in the HD injury pathway; however, they had no immediate or obvious effect on cell to substrate attachment.
Databáze: OpenAIRE
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