Dissertação
Influência do metabolismo do ATP extracelular na sinalização purinérgica em linfócitos e plaquetas de pacientes com a forma indeterminada da doença de chagas
Fecha
2011-07-15Registro en:
SOUZA, Viviane do Carmo Gonçalves. INFLUENCE OF EXTRACELLULAR ATP METABOLISM IN THE PURINERGIC SIGNALING IN LYMPHOCYTES AND PLATELETS OF PATIENTS WITH INDETERMINATE FORM OF CHAGAS DISEASE. 2011. 129 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2011.
Autor
Souza, Viviane do Carmo Gonçalves
Institución
Resumen
Trypanosoma cruzi infection causes Chagas disease (CD), a chronic inflammatory
disease. The most infected individuals present no apparent morbidity, consistent with the
indeterminate form of Chagas disease (IFCD). Although parasite-related factors may influence
the clinical progress of disease, factors such as immune and inflammatory responses of host
have a fundamental participation in the dynamic of pathology. The cellular immune response is
closely associated with the presence of a tissue inflammatory infiltrate, which is composed by
mononuclear cells that proliferate and produce pro- and anti-inflammatory cytokines. The
inflammatory reaction triggered by T. cruzi infection is maintained by persistence of parasite in
the host, and produces systemic effects, including microvascular changes. The puricergic
signaling system plays an important role in the modulatiib of immune and inflammatory responses
as well as vascular thrombosis by adenine nucleotides (ATP, ADP and AMP) and their derivative
nucleoside adenosine. These signaling molecules are released from cells such as lymphocytes
and platelets in response to damage or cell stimulation by the action of pathogens. The effects of
adenine nucleotides and adenosine are promoted through the agonism of specific purinergic
receptors and controlled by an enzymatic complex located on the cell surface. The aim of this
study was to evaluate the influence of purinergic signaling in the regulation of microvascular
dysfunction triggered by infection and in the adaptive immune response induced by the host
through ectoenzymes activities involved in the metabolism of ATP in lymphocytes and platelets of
patients IFCD. It was observed a decrease in both E-NTPDase and E-ADA activities,
representing an adaptive consequence of host to a low antigenic stimulation during the latent
phase of disease. Therefore, low concentrations of extracellular ATP would lead the induction of
a Th2 response that would protect the host from an intense Th1 response, while high
concentrations of extracellular adenosine would be responsible for anti-inflammatory and
immunosuppressive effects. It was not observed any change in E-NTPDase expression when
compared with the control group, demonstrating that its decreased activity may be a result of
some tridimencional alteration of the enzyme itself. In platelets of IFCD patients, there was an
increase in E-NPP and E-5 -NT activities and a decrease in E-ADA activity, which could be
related to tromboregulatory effects by nucleotides degradation as well as formation and
preservation of extracellular adenosine levels, in view of its vasodilator and cardioprotective roles.
The decreased platelet aggregation observed in IFCD patients probably occurred due to antiaggregating
action of adenosine. In conclusion, the purinergic system ectoenzymes, which are
responsible for ATP metabolism, contribute in tromborregulation and modulation of host immune
responses during the indeterminate form of the disease.