Accession Number:

ADA429624

Title:

Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur Mustard Injury to Human Skin

Descriptive Note:

Annual rept. 1 May 2003-30 Apr 2004

Corporate Author:

STATE UNIV OF NEW YORK AT STONY BROOK RESEARCH FOUNDATION

Personal Author(s):

Report Date:

2004-05-01

Pagination or Media Count:

70.0

Abstract:

We first measured dose-time responses in 2-D and 3-D cultures TASK 1 and discovered that an SM dose of 150 micronmeter induced significant apoptotic cell death. We next compared the SM response of 3-D cultures grown in the absence or presence AlloDerm of structured basement membrane BM TASK 8 and found that the presence of BM led to resistance to SM-induced damage, suggesting that BM could protect basal keratinocytes from SM-induced apoptosis. To further explore the role of BM in decreased SM susceptibility, primary keratinocytes harvested from Junctional Epidermolysis Bullosa JEB patients 552, that lack a functional gammaexp 2 chain of laminin 5 and do not adhere to BM, were transduced with retroviral vectors TASK 4 to restore or abrogate laminin 5-mediated adhesion. We constructed 3-D tissues with these reverted JEB cells TASK 5,6 and 7 and their phenotypic analysis showed that only JEB cells with restored laminin 5 function F-GAL were resistant to apoptosis when exposed to SM 150 micronmeter, thereby implicating laminin 5-mediated attachment as being important in limiting SM damage. These studies provide important evidence that bioengineered, in vitro tissues mimic many skin alterations previously found in vivo and that adhesion to BM enables epithelial resistance to SM damage.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE