Adenosine Deaminase Activities in Sera, Lymphocytes and Granulocytes in Patients with Cutaneous Leishmaniasis (original) (raw)
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PloS one, 2016
Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17....
Adenosine and Immune Imbalance in Visceral Leishmaniasis: The Possible Role of Ectonucleotidases
Journal of Tropical Medicine, 2012
Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is responsible for most Leishmania-associated deaths. VL represents a serious public health problem that affects many countries. The immune response in leishmaniasis is very complex and is poorly understood. The Th1 versus Th2 paradigm does not appear to be so clear in visceral leishmaniasis, suggesting that other immunosuppressive or immune-evasion mechanisms contribute to the pathogenesis of VL. It has been demonstrated that generation of adenosine, a potent endogenous immunosuppressant, by extracellular enzymes capable to hydrolyze adenosine trinucleotide (ATP) at the site of infection, can lead to immune impairment and contribute to leishmaniasis progression. In this regard, this paper discusses the unique features in VL immunopathogenesis, including a possible role for ectonucleotidases in leishmaniasis.
Cytokine, 2017
Adenosine, an endogenous purine nucleoside is one such extracellular signaling molecule whose role in the regulation of anti-inflammatory cytokines and immune pathogenicity in visceral leishmaniasis is indeterminate. Here, we have evaluated the adenosine in the plasma of 20 visceral leishmaniasis (VL) patients during active disease and after successful treatment. We observed the elevated plasma adenosine during active VL disease (26.73±1.95μM) and the level subsides as the treatment progresses and falls to the normal level after successful treatment (4.32±0.45μM). We demonstrated a direct correlation between changes in the plasma adenosine level and the Th1/Th2 balance in VL patients and it was corroborated with in vitro experiment. Further, we delineated the molecular mechanism involved in the elevation of plasma adenosine during visceral leishmaniasis. Our results reveal that the elevated plasma adenosine level associated with pathogenicity and plays a critical role in skewing imm...
Serum nitrite level and adenosine deaminase activity is altered in visceral leishmaniasis
Nepal Medical College journal : NMCJ, 2007
In this study we sought to determine if there is alteration in nitric oxide (NO) production and adenosine deaminase (ADA) activity among patients with visceral leishmaniasis (VL) and the effect of four weeks of chemotherapy on these levels. Fifty-three VL patients diagnosed clinically and by direct demonstration of the LD bodies in the bone marrow smear were studied. They were treated with Sodium Stibogluconate and sampled at the baseline and four weeks. Forty-three healthy individuals coming from the same endemic area were taken as control. Total nitrite (NO2- and NO3-) as an index of NO production and ADA activity was measured spectrophotometrically. Serum nitrite level decreased significantly in patients as compared to the healthy individuals but significantly increased following 4 weeks of chemotherapy. Conversely, Increased ADA activity was observed in the beginning of treatment and decreased significantly with successive 4 weeks of chemotherapy. It seems a negative correlation...
Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia
PLoS Neglected Tropical Diseases, 2012
Background: Cutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood.
Cytokine, 2015
Adenosine, an endogenous purine nucleoside is one such extracellular signalling molecule whose role in regulation of anti-inflammatory cytokines and immune pathogenicity in visceral leishmaniasis is not fully understood. Here, we investigated the relationship between Leishmania donovani infection and expression of A2B receptor on monocytes in VL patients in their pre and post treatment stage. We also investigated the molecular mechanisms influencing the interaction between immunopathogenicity and infection by exposing Leishmania donovani pulsed macrophages to Adenosine. A direct correlation of up-regulated A2B expression on monocytes with increased parasite load was also observed. Our results also suggested that A2B receptor activation is critically required for the stimulatory effect of adenosine on IL-10 production and suppression of nitric oxide release. The stimulatory effect of adenosine on Leishmania donovani induced IL-10 production required ERK1/2 activation and is p-38 MAPK...
Journal of Parasitic …, 2012
Intracellular pathogenic protozoan infection like visceral leishmaniasis is considered in terms of the overall inflammatory response and the complex cellular interactions leading to formation of the activated macrophage. Analysis of the development of activation is facilitated when operationally defined stage of activation are characterized using a library of objective markers. There is a role of arginase in the immune response supporting its involvement in macrophage effector mechanism in vitro and in vivo. 5 0 -Nucleotidase a plasma membrane component has been cited as a biochemical correlate of macrophage function in an altered morphological and biochemical state of activation and stimulation. Depression in 5 0 -nucleotidase activity has been generally referred to as a characteristic marker of activated macrophages. Lysozyme or lysosomal enzymes are released into the endocytic or autophagic vacuole macrophage where they serve the purpose of intracellular digestion of engulfed or segregated materials. In the present study, we have studied levels of arginase and 5 0 -nucleotidase (marker for macrophage activation) in monocytes of active VL patients and healthy controls. Lysozyme a secretary product of macrophages was also measured in supernatants collected from monocytes of active VL patients and healthy controls. Elevated levels of 5 0 -nucleotidase were observed in supernatants of monocytes from active VL patients as compared to healthy controls. Low levels of arginase and lysozyme production by monocytes isolated from VL patients were observed as compared to healthy controls. Our studies suggest that low levels of arginase and elevated 5 0 -nucleotidase activity could be one of the mechanisms in the pathology of VL infection. Low lysozyme activity in patients may account for persistence of Leishmania parasites in VL infections.
Clinical and Experimental Immunology, 2003
SUMMARY Lymphoproliferative responses to three affinity chromatography purified amastigote antigens of Leishmania pifanoi, P-2, P-4 and P-8, were evaluated in peripheral blood mononuclear cells (PBMC) from patients with Ethiopian cutaneous leishmaniasis. Antigen-stimulated cells were analysed for the percentage of CD4+, CD8+ and CD16/56+ cells and the expressed levels of gamma interferon (IFNγ) and interleukin (IL)-10 were determined in culture supernatants. The amastigote antigens induced cellular responses in leishmaniasis patients with heterologous Leishmania parasite infection. These responses were compared to those of freeze-thawed L. aethiopica promastigote antigen stimulation. The membrane protein (P-8), and to a lesser extent the megasomal/cytoplasmic cysteine proteinase(P-2), induced proliferation with high levels of IFNγ and IL-10 production in cells from patients with active L. aethiopica lesions. CD16/56+ NK cells were the main cell types induced to proliferate in respon...
Frontiers in cellular and infection microbiology, 2017
Infection by Leishmania protozoan parasites can cause a variety of disease outcomes in humans and other mammals, from single self-healing cutaneous lesions to a visceral dissemination of the parasite. The correlation between chronic lesions and ecto-nucleotidase enzymes activity on the surface of the parasite is addressed here using damage caused in epithelial cells by nitric oxide. In order to explore the role of purinergic metabolism in lesion formation and the outcome of the infection, we implemented a cellular automata/lattice gas model involving major immune characters (Th1 and Th2 cells, IFN-γ, IL-4, IL-12, adenosine-Ado-, NO) and parasite players for the dynamic analysis of the disease progress. The model were analyzed using partial ranking correlation coefficient (PRCC) to indicate the components that most influence the disease progression. Results show that low Ado inhibition rate over Th-cells is shared by L. major and L. braziliensis, while in L. amazonensis infection the...