Anti-Trypanosoma-cruzi-proteinase antibodies and immunoprotection in experimental Chagas' disease

Sakurada, Júlia Keiko; Maury, A.; Tamashiro, Wirla Maria da Silva Cunha; Araujo, Paulo Maria Ferreira de; Camargo, I. J. B.; Rangel, Humberto A.

doi:10.1016/s0923-2494(92)80158-h

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…Processes involved in macrophage infection with T. cruzi are extensively studied (12). The membrane cysteine proteinase cruzipain of T. cruzi, which corresponds to the major antigen gp 57/51 (13)(14)(15)(16)(17), has been shown to be involved in macrophage infection during the first step of the parasite-macrophage recognition using anti-cruzipain antibodies (18,19) and synthetic irreversible inhibitors of the cysteine proteinases (20,21).…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Cystatins Up-regulate Nitric Oxide Release from Interferon-γ- activated Mouse Peritoneal Macrophages

Verdot

Lalmanach

Vercruysse

et al. 1996

Journal of Biological Chemistry

102

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Up-regulation of nitric oxide (NO) production by activated murine macrophages was observed during infection by Trypanosoma cruzi, the etiological agent of Chagas' disease. Cell infection by T. cruzi depends at least in part on cruzipain, a membrane-associated papain-related proteinase which is sensitive to inhibition by synthetic inhibitors of cysteine proteinases. Using the natural cysteine proteinase inhibitor chicken cystatin, a representative member of cystatin family 2, to investigate the effect of cruzipain on macrophage infection and NO release, we found that the inhibitor alone up-regulated NO release from interferon-␥-activated macrophages. A 12-fold increase in NO production was observed in the presence of 1 M chicken cystatin. This overproduction was concentration-dependent and could be detected at concentrations as low as 10 nM and remained in the presence of polymyxin B. Representative members of the other cystatin families, i.e. stefin B (family 1), T-kininogen, and its inhibitory domains (family 3), were also able to enhance NO production from interferon-␥-activated macrophages. Neither E64, an irreversible inhibitor of cysteine proteinases, nor inhibitors of aspartyl and serine proteinases (aprotinin, pepstatin, and soybean trypsin inhibitor) enhanced NO production. Upon complexation with saturating amounts of reduced-alkylated papain, cystatins still remained active in increasing NO production, suggesting that the cystatin inhibitory site was not involved in the mechanism.The results demonstrate that members of all 3 cystatin families share another common property unrelated to their function of cysteine proteinase inhibitors, i.e. upregulation of NO production, which biological significance remains to be elucidated. Nitric oxide (NO)1 is a multipotent physiologic molecule detected in the immune, neuronal, and vascular systems and in many other tissues (1). NO is synthesized by a wide variety of cell types from L-arginine by NO synthases (NOS), three distinct isoforms of which have now been identified (2, 3). Two isoforms are constitutive and Ca 2ϩ -calmodulin dependent: the first is membrane-bound, and was initially discovered in endothelial cells; the second is soluble and was first identified in neurons. The third isoform is an inducible Ca 2ϩ -independent NOS first discovered in murine macrophages and induced by appropriate stimulation with cytokines (4 -7).Among other cells, macrophages allow the intracellular multiplication of Trypanosoma cruzi, the etiological agent of Chagas' disease, a major public health problem in South and Central America (8). A close relationship has been demonstrated between NO production in activated murine macrophages and T. cruzi infection (9). The parasite modulates the NO production by cytokine and LPS-activated macrophages (10, 11). Processes involved in macrophage infection with T. cruzi are extensively studied (12). The membrane cysteine proteinase cruzipain of T. cruzi, which corresponds to the major antigen gp 57/51 (13-17), has been shown to be involved i...

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Section: Nitric Oxide (No)mentioning

confidence: 99%

Cystatins Up-regulate Nitric Oxide Release from Interferon-γ- activated Mouse Peritoneal Macrophages

Verdot

Lalmanach

Vercruysse

et al. 1996

Journal of Biological Chemistry

102

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“…In addition, macrophages have a major role in the innate immunity and participate as effector cells in adaptative immune response. Cruzipain has been involved in macrophage infection during the first step of the parasite-macrophage recognition [15,16]. The classical metabolic pathway in which macrophages stimulated by Th1 cytokines possess cytotoxic and antimicrobial effector functions is based on the ability to produce nitric oxide [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite

Giordanengo¹,

Guiñazú²,

Stempin³

et al. 2002

Eur. J. Immunol.

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We recently demonstrated that humoral immune response to cruzipain, a major antigen of Trypanosoma cruzi parasite, is implicated in the pathogenesis of experimental Chagas' disease. In the present study, the spleen cell phenotype and the cytokine profile induced by cruzipain in immunized mice were analyzed. The results showed that cruzipain increases the number of spleen cells with large size and granularity. Splenocyte populations with CD19 + , Mac-1 + , Gr-1 + and CD11c + positive surface markers significantly increased in immune mice compared to controls ones. Histological study revealed the presence of high number of megacariocyte and granulocyte-macrophage progenitors, indicating extramedullary hemopoiesis in spleens of immune mice. The finding of high levels of IL-4, IL5 and IL-10 and low levels of IFN-+ and IL-12 in supernatants of immune cells stimulated with cruzipain indicates a preferential activation of T2 type cells in immune animals. To investigate the role of innate immunity cells, the classical and alternative metabolic pathways of spleen macrophages from immune mice stimulated by cruzipain were also studied. The results showed an increase of urea associated with a decrease of nitrite levels, suggesting that cruzipain upregulates the arginase way. Therefore, cruzipain leads to T2 type cytokine profile which may enhance the arginase via in the macrophages promoting a susceptible mechanism to infection. Thus, we postulate that during T. cruzi infection, cruzipain could be used by the parasite to spread inside the host.

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Cruzipain, a majorTrypanosoma cruziantigen, conditions the host immune response in favor of parasite

et al. 2002

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Anti-Trypanosoma-cruzi-proteinase antibodies and immunoprotection in experimental Chagas' disease

Cited by 4 publications

References 30 publications

Cystatins Up-regulate Nitric Oxide Release from Interferon-γ- activated Mouse Peritoneal Macrophages

Cystatins Up-regulate Nitric Oxide Release from Interferon-γ- activated Mouse Peritoneal Macrophages

Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite

Cruzipain, a majorTrypanosoma cruziantigen, conditions the host immune response in favor of parasite

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