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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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