The parasitic protozoan Trypanosoma cruzi employs multiple molecular strategies to invade a broad range of nonphagocytic cells. Here we demonstrate that the invasion of human primary umbilical vein endothelial cells (HUVECs) or Chinese hamster ovary (CHO) cells overexpressing the B2 type of bradykinin receptor (CHO-B2R) by tissue culture trypomastigotes is subtly modulated by the combined activities of kininogens, kininogenases, and kinin-degrading peptidases. The presence of captopril, an inhibitor of bradykinin degradation by kininase II, drastically potentiated parasitic invasion of HUVECs and CHO-B2R, but not of mock-transfected CHO cells, whereas the B2R antagonist HOE 140 or monoclonal antibody MBK3 to bradykinin blocked these effects. Invasion competence correlated with the parasites' ability to liberate the short-lived kinins from cell-bound kininogen and to elicit vigorous intracellular free calcium ([Ca2+]i) transients through B2R. Invasion was impaired by membrane-permeable cysteine proteinase inhibitors such as Z-(SBz)Cys-Phe-CHN2 but not by the hydrophilic inhibitor 1-trans-epoxysuccinyl-l-leucyl-amido-(4-guanidino) butane or cystatin C, suggesting that kinin release is confined to secluded spaces formed by juxtaposition of host cell and parasite plasma membranes. Analysis of trypomastigote transfectants expressing various cysteine proteinase isoforms showed that invasion competence is linked to the kinin releasing activity of cruzipain, herein proposed as a factor of virulence in Chagas' disease.
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6 November 2000
Article|
November 06 2000
Host Cell Invasion by TRYPANOSOMA cRUZI Is Potentiated by Activation of Bradykinin B2 Receptors
Julio Scharfstein,
Julio Scharfstein
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
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Veronica Schmitz,
Veronica Schmitz
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
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Veronica Morandi,
Veronica Morandi
bDepartment of Cell Biology and Genetics, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-013, Brazil
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Marcia M. A. Capella,
Marcia M. A. Capella
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
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Ana Paula C. A. Lima,
Ana Paula C. A. Lima
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
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Alexandre Morrot,
Alexandre Morrot
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
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Luiz Juliano,
Luiz Juliano
cDepartment of Biophysics, Escola Paulista de Medicina-Universidade Federal de São Paolo, São Paulo 04044-000, Brazil
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Werner Müller-Esterl
Werner Müller-Esterl
dInstitute for Biochemistry II, University of Frankfurt Medical School, D-60590 Frankfurt, Germany
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Julio Scharfstein
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
Veronica Schmitz
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
Veronica Morandi
bDepartment of Cell Biology and Genetics, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-013, Brazil
Marcia M. A. Capella
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
Ana Paula C. A. Lima
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
Alexandre Morrot
aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990-400 Rio de Janeiro, Brazil
Luiz Juliano
cDepartment of Biophysics, Escola Paulista de Medicina-Universidade Federal de São Paolo, São Paulo 04044-000, Brazil
Werner Müller-Esterl
dInstitute for Biochemistry II, University of Frankfurt Medical School, D-60590 Frankfurt, Germany
Abbreviations used in this paper: ACE, angiotensin I–converting enzyme; BK, bradykinin; [CA2+]i, intracellular free calcium; CHO, Chinese hamster ovary; DTT, dithiothreitol; H-kininogen, high molecular weight kininogen; HUVEC, human primary umbilical vein endothelial cell; TCT, tissue culture trypomastigote.
Received:
February 07 2000
Revision Requested:
September 27 2000
Accepted:
September 28 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (9): 1289–1300.
Article history
Received:
February 07 2000
Revision Requested:
September 27 2000
Accepted:
September 28 2000
Citation
Julio Scharfstein, Veronica Schmitz, Veronica Morandi, Marcia M. A. Capella, Ana Paula C. A. Lima, Alexandre Morrot, Luiz Juliano, Werner Müller-Esterl; Host Cell Invasion by TRYPANOSOMA cRUZI Is Potentiated by Activation of Bradykinin B2 Receptors. J Exp Med 6 November 2000; 192 (9): 1289–1300. doi: https://doi.org/10.1084/jem.192.9.1289
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