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Diagnosis of Sulfur Mustard Exposure Based On Epidermal‐Dermal Junction Proteins (Laminin‐5, Integrin) Degradation
Author(s) -
Jin Xiannu,
Ray Radharaman,
Cao Ying,
Ray Prabhati
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a515-e
Subject(s) - laminin , integrin , immunofluorescence , chemistry , blot , in vivo , sulfur mustard , microbiology and biotechnology , western blot , biochemistry , antibody , immunology , biology , toxicity , receptor , extracellular matrix , organic chemistry , gene
Sulfur mustard (SM, 2, 2′‐dichlorodiethyl sulfide) is an alkylating vesicant agent. The injuries due to SM are mainly characterized by epithelial damage in exposed tissues such as the skin. In the skin, proteins mostly affected by SM‐exposure are laminin‐5 and integrin‐alpha6beta4. Laminin‐5 and integrin‐alpha6beta4 constitute the attachment protein complex responsible for epidermal‐dermal adhesion. Here, we studied SM specificity, time‐course and dose‐response for degradation of both laminin‐5 and integrin‐á6â4 by E‐PAGE Western blotting and immunofluorescence staining methods utilizing laminin‐5 (beta3 or gamma2 subunit) and integrin‐alpha6beta4 antibodies. In the in vitro skin model of cultured normal human epidermal keratinocytes (NHEK), SM degraded both laminin‐5 and integrin‐á6â4 in a concentration (50–300 ìM)‐ and time (1–16 hour)‐dependent manner. The laminin‐5 (gamma2) degradation effect was specific for SM and not for the other alkylating agents tested. Using the Western blotting method, we also validated the SM‐induced laminin‐5 (gamma2) degradation in vivo in SM vapor cup‐exposed hairless guinea pig and mouse skin samples. These results suggest the possibility of utilizing laminin‐5 and integrin á6â4 as biomarkers for mustard exposure diagnosis.