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Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection.

Publication ,  Journal Article
Ashton, AW; Mukherjee, S; Nagajyothi, FNU; Huang, H; Braunstein, VL; Desruisseaux, MS; Factor, SM; Lopez, L; Berman, JW; Wittner, M; Capra, V ...
Published in: J Exp Med
April 16, 2007

Chagas' disease is caused by infection with the parasite Trypanosoma cruzi. We report that infected, but not uninfected, human endothelial cells (ECs) released thromboxane A(2) (TXA(2)). Physical chromatography and liquid chromatography-tandem mass spectrometry revealed that TXA(2) is the predominant eicosanoid present in all life stages of T. cruzi. Parasite-derived TXA(2) accounts for up to 90% of the circulating levels of TXA(2) in infected wild-type mice, and perturbs host physiology. Mice in which the gene for the TXA(2) receptor (TP) has been deleted, exhibited higher mortality and more severe cardiac pathology and parasitism (fourfold) than WT mice after infection. Conversely, deletion of the TXA(2) synthase gene had no effect on survival or disease severity. TP expression on somatic cells, but not cells involved in either acquired or innate immunity, was the primary determinant of disease progression. The higher intracellular parasitism observed in TP-null ECs was ablated upon restoration of TP expression. We conclude that the host response to parasite-derived TXA(2) in T. cruzi infection is possibly an important determinant of mortality and parasitism. A deeper understanding of the role of TXA(2) may result in novel therapeutic targets for a disease with limited treatment options.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 16, 2007

Volume

204

Issue

4

Start / End Page

929 / 940

Location

United States

Related Subject Headings

  • Trypanosoma cruzi
  • Thromboxane A2
  • Signal Transduction
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans
  • GTP-Binding Protein alpha Subunits, Gq-G11
 

Citation

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Ashton, A. W., Mukherjee, S., Nagajyothi, F. N. U., Huang, H., Braunstein, V. L., Desruisseaux, M. S., … Tanowitz, H. B. (2007). Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection. J Exp Med, 204(4), 929–940. https://doi.org/10.1084/jem.20062432
Ashton, Anthony W., Shankar Mukherjee, F. N. U. Nagajyothi, Huan Huang, Vicki L. Braunstein, Mahalia S. Desruisseaux, Stephen M. Factor, et al. “Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection.J Exp Med 204, no. 4 (April 16, 2007): 929–40. https://doi.org/10.1084/jem.20062432.
Ashton AW, Mukherjee S, Nagajyothi FNU, Huang H, Braunstein VL, Desruisseaux MS, et al. Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection. J Exp Med. 2007 Apr 16;204(4):929–40.
Ashton, Anthony W., et al. “Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection.J Exp Med, vol. 204, no. 4, Apr. 2007, pp. 929–40. Pubmed, doi:10.1084/jem.20062432.
Ashton AW, Mukherjee S, Nagajyothi FNU, Huang H, Braunstein VL, Desruisseaux MS, Factor SM, Lopez L, Berman JW, Wittner M, Scherer PE, Capra V, Coffman TM, Serhan CN, Gotlinger K, Wu KK, Weiss LM, Tanowitz HB. Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection. J Exp Med. 2007 Apr 16;204(4):929–940.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 16, 2007

Volume

204

Issue

4

Start / End Page

929 / 940

Location

United States

Related Subject Headings

  • Trypanosoma cruzi
  • Thromboxane A2
  • Signal Transduction
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans
  • GTP-Binding Protein alpha Subunits, Gq-G11