Inducible Nitric Oxide Synthase and Arginase Expression in Heart Tissue during

CUERVO H, PINEDA MA, AOKI MP, GEA S, FRESNO M, GIRONÈS N.

JOURNAL OF INFECTIOUS DISEASES

Año: 2008 vol. 179 p. 1772 - 1782

0022-1899

In Chagas disease, which is caused by Trypanosoma cruzi, macrophages andcardiomyocytes are the main targets of infection. Classical activation ofmacrophages during infection is protective, whereas alternative activation ofmacrophages is involved in the survival of host cells and parasites. We studiedthe expression of inducible nitric oxide synthase (iNOS) and arginase as markers of classical and alternative activation, respectively, in heart tissue during in vivo infection of BALB/c and C57BL/6 mice. We found that expression of arginase Iand II, as well as that of ornithine decarboxylase, was much higher in BALB/cmice than in C57BL/6 mice and that it was associated with the parasite burden in heart tissue. iNOS and arginase II were expressed by cardiomyocytes.Interestingly, heart-infiltrated CD68(+) macrophages were the major cell typeexpressing arginase I. T helper (Th) 1 and Th2 cytokines were expressed in heart tissue in both infected mouse strains; however, at the peak of parasiteinfection, the balance between Th1 and Th2 predominantly favored Th1 in C57BL/6mice and Th2 in BALB/c mice. The results of the present study suggest that Th2cytokines induce arginase expression, which may influence host and parasite cell survival but which might also down-regulate the counterproductive effectstriggered by iNOS in the heart during infection.