ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry: Implications for the pathogenesis of anthrax infection

Gloria Bonuccelli, Federica Sotgia, Philippe G. Frank, Terence M. Williams, Cecilia J. De Almeida, Herbert B. Tanowitz, Philipp E. Scherer, Kylie A. Hotchkiss, Bruce I. Terman, Brent Rollman, Abdelkrim Alileche, Jürgen Brojatsch, Michael P. Lisanti

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Anthrax is a disease caused by infection with spores from the bacteria Bacillus anthracis. These spores enter the body, where they germinate into bacteria and secrete a tripartite toxin that causes local edema and, in systemic infections, death. Recent studies identified the cellular receptor for anthrax toxin (ATR), a type I membrane protein. ATR is one of the splice variants of the tumor endothelial marker 8 (TEM8) gene. ATR and TEM8 are identical throughout their extracellular and transmembrane sequence, and both proteins function as receptors for the toxin. ATR/TEM8 function and expression have been associated with development of the vascular system and with tumor angiogenesis: TEM8 is selectively upregulated in endothelial cells during blood vessel formation and tumorigenesis. However, selective expression of TEM8 in endothelial cells contradicts the presumably ubiquitous expression of the receptor. To resolve this controversial issue, we evaluated the distribution of ATR/TEM8 in a variety of tissues. For this purpose, we generated and characterized a novel anti-ATR/TEM8 polyclonal antibody. Here, we show that this novel antibody recognizes all three ATR/TEM8 isoforms, which are widely and differentially expressed in various tissue types. We found that ATR/TEM8 expression is not only associated with tumor endothelial cells, as previously described. Indeed, ATR/TEM8 is highly and selectively expressed in the epithelial cells lining those organs that constitute the anthrax toxin's sites of entry, i.e., the lung, the skin, and the intestine. In fact, we show that ATR/TEM8 is highly expressed in the respiratory epithelium of the bronchi of the lung and is particularly abundant in the ciliated epithelial cells coating the bronchi. Furthermore, immunostaining of skin biopsies revealed that ATR/TEM8 is highly expressed in the keratinocytes of the epidermis. Finally, we show that the epithelial cells lining the small intestine strongly express ATR/TEM8 isoforms. This is the first demonstration that the ATR/TEM8 protein is highly expressed in epithelial cells, which represent the primary location for bacterial invasion. These results suggest that the ATR/TEM8 expression pattern that we describe here is highly relevant for understanding the pathogenesis of anthrax infection.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume288
Issue number6 57-6
DOIs
StatePublished - Jun 2005

Fingerprint

Bacillus anthracis
Anthrax
Bacilli
Tumor Biomarkers
Linings
Tumors
Epithelial Cells
Infection
Endothelial cells
Endothelial Cells
anthrax toxin
Bronchi
Spores
Blood Vessels
Protein Isoforms
Bacteria
Skin
Respiratory Mucosa
Lung
Tissue

Keywords

  • Anthrax
  • Bacterial pathogenesis
  • Epithelia
  • Intestine
  • Lung
  • Receptor
  • Skin
  • Toxin entry

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry : Implications for the pathogenesis of anthrax infection. / Bonuccelli, Gloria; Sotgia, Federica; Frank, Philippe G.; Williams, Terence M.; De Almeida, Cecilia J.; Tanowitz, Herbert B.; Scherer, Philipp E.; Hotchkiss, Kylie A.; Terman, Bruce I.; Rollman, Brent; Alileche, Abdelkrim; Brojatsch, Jürgen; Lisanti, Michael P.

In: American Journal of Physiology - Cell Physiology, Vol. 288, No. 6 57-6, 06.2005.

Research output: Contribution to journalArticle

Bonuccelli, G, Sotgia, F, Frank, PG, Williams, TM, De Almeida, CJ, Tanowitz, HB, Scherer, PE, Hotchkiss, KA, Terman, BI, Rollman, B, Alileche, A, Brojatsch, J & Lisanti, MP 2005, 'ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry: Implications for the pathogenesis of anthrax infection', American Journal of Physiology - Cell Physiology, vol. 288, no. 6 57-6. https://doi.org/10.1152/ajpcell.00582.2004
Bonuccelli, Gloria ; Sotgia, Federica ; Frank, Philippe G. ; Williams, Terence M. ; De Almeida, Cecilia J. ; Tanowitz, Herbert B. ; Scherer, Philipp E. ; Hotchkiss, Kylie A. ; Terman, Bruce I. ; Rollman, Brent ; Alileche, Abdelkrim ; Brojatsch, Jürgen ; Lisanti, Michael P. / ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry : Implications for the pathogenesis of anthrax infection. In: American Journal of Physiology - Cell Physiology. 2005 ; Vol. 288, No. 6 57-6.
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T2 - Implications for the pathogenesis of anthrax infection

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AU - Sotgia, Federica

AU - Frank, Philippe G.

AU - Williams, Terence M.

AU - De Almeida, Cecilia J.

AU - Tanowitz, Herbert B.

AU - Scherer, Philipp E.

AU - Hotchkiss, Kylie A.

AU - Terman, Bruce I.

AU - Rollman, Brent

AU - Alileche, Abdelkrim

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AU - Lisanti, Michael P.

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KW - Skin

KW - Toxin entry

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