Accession Number:

ADB223904

Title:

The Cytoskeleton & ATP in Sulfur Mustard-Mediated Injury to Endothelial Cells & Keratinocytes.

Descriptive Note:

Final rept. 1 Jul 93-30 Sep 96,

Corporate Author:

VETERANS ADMINISTRATION HOSPITAL ANN ARBOR MI

Personal Author(s):

Report Date:

1996-12-01

Pagination or Media Count:

46.0

Abstract:

The goal of this project has been to define the nature of the cytopathology induced by sulfur mustard SM in endothelial cells and keratinocytes which accounts for vesication. Using fluorescence microscopic techniques and biochemical assays we tested the hypotheses that SM injury can cause two forms of cell death in endothelial cells and keratinocytes, apoptosis and necrosis, and that they result in cytoskeletal and morphologic changes which account for SM-induced blister formation. SM induced apoptosis and necrosis in endothelial cells, but only caused necrosis in keratinocytes. Minimal cell death was seen in keratinocytes with 250 M SM, which did cause apoptosis in endothelial cells. Actin filament disassembly or depolymerization was a common feature of injury in both cell types. SM-mediated alterations in microfilament organization and cellular shape correlated well with loss of cellular adherence and endothelial permeability barrier function. SM caused reductions in ATP and NAD in both cell types, but was associated with increased poly-ADP-ribose-polymerase activity only in endothelial cells. Polyacrylamide gel electrophoretic-analysis of cytoskeletal extracts under non-reducing conditions and measurements of glutathione provided evidence for an oxidative challenge during SM injury in keratinocytes. Thus, SM induces two very different patterns of cell injury in keratinocytes and endothelial cells. Cytoskeletal pathology common to both patterns of injury may be critical to the pathogenesis of vesication.

Subject Categories:

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

Distribution Statement:

APPROVED FOR PUBLIC RELEASE