Impaired frequencies and function of platelets and tissue remodeling in chronic Chagas disease

Abstract

Chronic inflammation, as a consequence of the persistent infection with Trypanosoma cruzi , leads to continuous activation of the immune system in patients with chronic Chagas disease. We have previously shown that increased sera levels of soluble P-selectin are associated with the severity of the cardiomyopathy distinctive of chronic Chagas disease. In this study, we explored the expression of biomarkers of platelet and endothelial activation, tissue remodeling, and mediators of the coagulation cascade in patients at different clinical stages of chronic Chagas heart disease. The frequencies of activated platelets, measured by the expression of CD41a and CD62P were decreased in patients with chronic Chagas disease compared with those in uninfected subjects, with an inverse association with disease severity. Platelet activation in response to adenosine diphosphate was also decreased in T . cruzi -infected subjects. A major proportion of T . cruzi infected subjects showed increased serum levels of fibrinogen. Patients with severe cardiac dysfunction showed increased levels of endothelin-1 and normal values of procollagen I. In conclusion, chronic infection with T . cruzi induced hemostatic alterations, even in those patients who do not yet present cardiac symptoms.

Immunomodulation and Antioxidant Activities as Possible Trypanocidal and Cardioprotective Mechanisms of Major Terpenes from Lippia alba Essential Oils in an Experimental Model of Chronic Chagas Disease

“…In hemogram analysis, a significant thrombocytosis ( p < 0.005) was reported for both the LIMOX and LIMOXBNZ therapies. Interestingly, platelet counts in peripheral blood have been inversely associated with disease severity in patients with CCC [ 31 ]. In this regard, platelets play an important role in immune response, including protective functions via the release of chemokines that attract and activate leukocytes and, at the same time, platelet surface molecules such as P-selectin and GPIIB/IIIa (Glycoprotein IIb/IIIa) [ 31 ].…”

“…Interestingly, platelet counts in peripheral blood have been inversely associated with disease severity in patients with CCC [ 31 ]. In this regard, platelets play an important role in immune response, including protective functions via the release of chemokines that attract and activate leukocytes and, at the same time, platelet surface molecules such as P-selectin and GPIIB/IIIa (Glycoprotein IIb/IIIa) [ 31 ]. Likewise, atypical lymphocytes were observed in the peripheral blood smear analysis of all infected animals (experimental groups and positive control) with the highest percentage of these reactive cells in BNZ-treated rats (10.8% for BNZ vs. 3.8% for positive control and 2% for LIMOXBNZ and LIMOX).…”

“…Likewise, atypical lymphocytes were observed in the peripheral blood smear analysis of all infected animals (experimental groups and positive control) with the highest percentage of these reactive cells in BNZ-treated rats (10.8% for BNZ vs. 3.8% for positive control and 2% for LIMOXBNZ and LIMOX). These cells are produced after a strong process of antigenic stimulation and stress, being classified as a nonspecific response to stimulus or as precursors of memory T and B cells [ 31 ]. However, a low percentage of these cells can normally be found in peripheral blood (2–6%) [ 32 ], thus the abnormally elevated percentages observed in BNZ therapy could be a reflex to its toxicity.…”

Innate immune receptors in platelets and platelet-leukocyte interactions

“…5B and C). A common feature of these diseases is thrombocytopenia, 238,328–331 which associates with the severity of each disease 321,329–332 . Thrombocytopenia may be related with increased platelet activation in these infections 333,334 .…”

“…A common feature of these diseases is thrombocytopenia, 238,[328][329][330][331] which associates with the severity of each disease. 321,[329][330][331][332] Thrombocytopenia may be related with increased platelet activation in these infections. 333,334 Higher levels of sP-selectin associated with the onset of cardiac disease in chronic chagasic patients.…”