Skip to main content
main-content

01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Piero Bagnaresi, Nilana MT Barros, Diego M Assis, Pollyana MS Melo, Raphael G Fonseca, Maria A Juliano, João B Pesquero, Luiz Juliano, Philip J Rosenthal, Adriana K Carmona, Marcos L Gazarini
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-156) contains supplementary material, which is available to authorized users.
Piero Bagnaresi, Nilana MT Barros contributed equally to this work.

Competing interests

The authors declare that they have no competing interest.

Authors’ contributions

PB carried out the confocal microscopy experiments, participated on the design of the study and drafted the manuscript. NMTB carried out the ileum contractions assays, participated on the design of the study and drafted the manuscript. DMA carried out the spectrometry analysis. PMSM participated in spectrometry assays and microscopy. RPG, JBP, MAJ, LJ and PJR participated in the design of the study. AKC and MLG conceived and coordinated the study, and helped to draft the manuscript. All authors read and approved the final manuscript.

Abstract

Background

The malaria burden remains a major public health concern, especially in sub-Saharan Africa. The complex biology of Plasmodium, the apicomplexan parasite responsible for this disease, challenges efforts to develop new strategies to control the disease. Proteolysis is a fundamental process in the metabolism of malaria parasites, but roles for proteases in generating vasoactive peptides have not previously been explored.

Results

In the present work, it was demonstrated by mass spectrometry analysis that Plasmodium parasites (Plasmodium chabaudi and Plasmodium falciparum) internalize and process plasma kininogen, thereby releasing vasoactive kinins (Lys-BK, BK and des-Arg9-BK) that may mediate haemodynamic alterations during acute malaria. In addition, it was demonstrated that the P. falciparum cysteine proteases falcipain-2 and falcipain-3 generated kinins after incubation with human kininogen, suggesting that these enzymes have an important role in this process. The biologic activity of peptides released by Plasmodium parasites was observed by measuring ileum contraction and activation of kinin receptors (B1 and B2) in HUVEC cells; the peptides elicited an increase in intracellular calcium, measured by Fluo-3 AM fluorescence. This effect was suppressed by the specific receptor antagonists Des-Arg9[Leu8]-BK and HOE-140.

Conclusions

In previously undescribed means of modulating host physiology, it was demonstrated that malaria parasites can generate active kinins by proteolysis of plasma kininogen.
Zusatzmaterial
Authors’ original file for figure 1
12936_2012_2117_MOESM1_ESM.jpeg
Authors’ original file for figure 2
12936_2012_2117_MOESM2_ESM.jpeg
Authors’ original file for figure 3
12936_2012_2117_MOESM3_ESM.jpeg
Authors’ original file for figure 4
12936_2012_2117_MOESM4_ESM.tiff
Authors’ original file for figure 5
12936_2012_2117_MOESM5_ESM.jpeg
Authors’ original file for figure 6
12936_2012_2117_MOESM6_ESM.jpeg
Authors’ original file for figure 7
12936_2012_2117_MOESM7_ESM.jpeg
Authors’ original file for figure 8
12936_2012_2117_MOESM8_ESM.jpeg
Authors’ original file for figure 9
12936_2012_2117_MOESM9_ESM.tiff
Authors’ original file for figure 10
12936_2012_2117_MOESM10_ESM.tiff
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2012

Malaria Journal 1/2012 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise