2024-03-28T22:35:46Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/83412016-02-16T04:01:26Zcom_10261_79com_10261_1col_10261_836
http://hdl.handle.net/10261/8341
7423
Metabolismo de la L-arginina en la enfermedad de Chagas experimental: papel de la arginasa I y la iNOS en tejido cardiaco
Universidad Autónoma de Madrid
2008
tesis doctoral
Cuervo, Henar
Tripanosomiasis americana
Metabolismo de aminoácidos
2008
Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular . Fecha de lectura: 25-04-2008
In Chagas disease, caused by Trypanosoma cruzi, macrophages and
cardiomyocytes are the main targets of infection. On the other hand, macrophages can
be activated in different ways by Th1 or Th2 cytokines leading to classic or alternative
activation, which results in different functional outcomes. Those different ways are
often differentiated by the expression of enzymes involved in L-arginine metabolism.
Thus, we studied the expression of such enzymes in heart tissue during in vivo infection
of BALB/c and C57BL/6 mice. We found that expression of inducible nitric oxide
synthase (iNOS), arginase I and II as well as ornithine decarboxylase, were much higher
in BALB/c compared to C57BL/6 mice and related to parasite burden in heart tissue.
Th1 and Th2 cytokines were expressed in heart tissue in both infected mouse strains,
but the Th1/Th2 balance was predominantly Th1 in C57BL/6 mice and Th2 in BALB/c
mice at the peak of parasite infection. By using mice strains genetically deficient in
various cytokines or their receptors, we found that IL-13, probably in cooperation with
IL-4, IL-10 and prostaglandin E2, induces arginase I expression. Inducible nitric oxide
synthase and arginase II were expressed by cardiomyocytes. Interestingly, heart
infiltrated CD68+ macrophages were the major cell type expressing arginase I. When
purified, CD11b+ heart infiltrating cells expressing both arginase I and iNOS did not
present a clear M1/M2 polarization but showed a myeloid suppressor cell phenotype. In
addition, these CD11b+ cells modulated T cell proliferation in vitro. Thus, arginase I
expression may influence parasite cell survival, and might be also regulating the
inflammatory T cell response in heart during infection.
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