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Infection and Immunity, June 1999, p. 3026-3030, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Anthrax Toxin Entry into Polarized Epithelial
Cells
Kathryn E.
Beauregard,1
Susan
Wimer-Mackin,2,3
R. John
Collier,1,4 and
Wayne I.
Lencer2,3,4,*
Departments of
Microbiology1 and
Pediatrics,2 Harvard Medical School,
Combined Program in Pediatric Gastroenterology and Nutrition,
Children's Hospital,3 and The Harvard
Digestive Diseases Center,4 Boston,
Massachusetts
Received 25 January 1999/Returned for modification 3 March
1999/Accepted 16 March 1999
We examined the entry of anthrax edema toxin (EdTx) into polarized
human T84 epithelial cells using cyclic AMP-regulated Cl
secretion as an index of toxin entry. EdTx is a binary A/B toxin which
self assembles at the cell surface from anthrax edema factor and
protective antigen (PA). PA binds to cell surface receptors and
delivers EF, an adenylate cyclase, to the cytosol. EdTx elicited a
strong Cl
secretory response when it was applied to the
basolateral surface of T84 cells but no response when it was applied to
the apical surface. PA alone had no effect when it was applied to
either surface. T84 cells exposed basolaterally bound at least
30-fold-more PA than did T84 cells exposed apically, indicating that
the PA receptor is largely or completely restricted to the basolateral membrane of these cells. The PA receptor did not fractionate with detergent-insoluble caveola-like membranes as cholera toxin receptors do. These findings have implications regarding the nature of the PA
receptor and confirm the view that EdTx and CT coopt fundamentally different subcellular systems to enter the cell and cause disease.
*
Corresponding author. Mailing address: GI Cell Biology,
Enders 1220, Children's Hospital, 300 Longwood Ave., Boston, MA 02115. Phone: (617) 355-8599. Fax: (617) 730-0404. E-mail:
lencer{at}a1.tch.harvard.edu.
Infection and Immunity, June 1999, p. 3026-3030, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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