Effect of the Synadenium carinatum latex lectin (ScLL) on Leishmania (Leishmania) amazonensis infection in murine macrophages.

Antiparasitic effect of a lectin isolated from Synadenium carinatum latex (ScLL) was evaluated against Leishmania (Leishmania) amazonensis promastigotes/amastigotes. Pretreatment of murine inflammatory peritoneal macrophages with ScLL reduced by 65.5% the association index of macrophages and L. (L) amazonensis promastigotes. Expression of cytokines (IL-12, IL-1 and TNF-α) was detected in infected macrophages pretreated with ScLL (10µg/mL). ScLL also reduced the growth of L. (L) amazonensis amastigote intracellular forms, showing no in vitro cytotoxic effects in mammalian host cells. ScLL treatment in infected murine inflammatory peritoneal macrophages did not induce nitric oxide production, suggesting that a nitric oxide independent pathway is activated to decrease the number of intracellular Leishmania.

Anti-asthmatic potential of a D-galactose-binding lectin from Synadenium carinatum latex.

Extracts from the plant Synadenium carinatum latex are widely and indiscriminately used in popular medicine to treat a great number of inflammatory disorders and although the mechanisms underlying these effects remain undefined, the lectin isolated from S. carinatum latex (ScLL) is thought to be in part responsible for these anti-inflammatory effects. In order to elucidate possible immunoregulatory activities of ScLL, we investigated the effects of ScLL administration in models of acute and chronic inflammation. Oral administration of ScLL significantly inhibited neutrophil and eosinophil extravasation in models of acute and chronic inflammation and reduced eosinophil and mononuclear blood counts during chronic inflammation. ScLL administration reduced IL(interleukin)-4 and IL-5 levels but increased interferon-gamma and IL-10 in an asthma inflammatory model, which suggested that it might induce a TH2 to TH1 shift in the adaptive immune response. ScLL also inhibited IkappaBalpha degradation, a negative regulator of proinflammatory NF-kappaB. Taken together, these results provide the first description of a single factor isolated from S. carinatum latex extract with immunoregulatory functions and suggest that ScLL may be useful in the treatment of allergic inflammatory disorders.

Protective effect of lectin from Synadenium carinatum on Leishmania amazonensis infection in BALB/c mice.

The protective effect of the Synadenium carinatum latex lectin (ScLL), and the possibility of using it as an adjuvant in murine model of vaccination against American cutaneous leishmaniasis, were evaluated. BALB/c mice were immunized with the lectin ScLL (10, 50, 100 microgram/animal) separately or in association with the soluble Leishmania amazonensis antigen (SLA). After a challenge infection with 10(6) promastigotes, the injury progression was monitored weekly by measuring the footpad swelling for 10 weeks. ScLL appeared to be capable of conferring partial protection to the animals, being most evident when ScLL was used in concentrations of 50 and 100 microgram/animal. Also the parasite load in the interior of macrophages showed significant reduction (61.7%) when compared to the control group. With regard to the cellular response, ScLL 50 and 100 microgram/animal stimulated the delayed-type hypersensitivity (DTH) reaction significantly (P < 0.05) higher than SLA or SLA plus ScLL 10 weeks after the challenge infection. The detection of high levels of IgG2a and the expression of mRNA cytokines, such as IFN-gamma, IL-12, and TNF-alpha (Th1 profiles), corroborated the protective role of this lectin against cutaneous leishmaniasis. This is the first report of the ScLL effect on leishmaniasis and shows a promising role for ScLL to be explored in other experimental models for treatment of leishmaniasis.

Levels of immunoglobulin A1 and messenger RNA for interferon gamma and tumor necrosis factor alpha in total saliva from patients with diabetes mellitus type 2 with chronic periodontal disease.

BACKGROUND: Diabetes mellitus and periodontal disease have high incidence in the general population and are associated with various degrees of dysfunction in the immune system. It has been shown that diabetic patients with severe periodontal disease have more complications of diabetes and less effective metabolic control compared with diabetic patients with healthy gingiva. Patients with diabetes and severe periodontal disease present higher levels of serous immunoglobulin A (IgA). Elevation of the IgA1 isotype is thought to contribute to this phenomenon. Another important event in the diabetes-periodontitis association is the disturbance in local and systemic production of inflammatory cytokines. OBJECTIVE: In this study we tested the hypothesis that type 2 diabetic patients with chronic moderate periodontal disease have differences in salivary IgA1 titers and cytokine expression when compared with the chronic severe periodontal disease cases. METHODS: We utilized a jacalin-IgA capture assay to determine the IgA1 titers in total saliva and reverse transcriptase-polymerase chain reaction to detect mRNA for interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in total saliva samples of 13 patients with chronic moderate periodontal disease and 10 with chronic severe periodontal disease. RESULTS AND CONCLUSIONS: We observed a predominance of IgA1 titers of 64 (45.5%) in saliva samples from chronic severe periodontal disease patients and titers averaging 512 (30.8%) in chronic moderate periodontal disease patients. We detected mRNA for IFN-gamma in six out of 10 chronic severe periodontal disease subjects and in two out of 13 chronic moderate periodontal disease patients. TNF-alpha expression was similar in both groups. Our data suggest that higher levels of IgA1 may exert partial protection of the periodontal tissue in chronic moderate periodontal disease diabetic patients when compared to severe periodontal disease. Despite the small number of patients, IFN-gamma expression had a trend association with severity of periodontitis and TNF-alpha gene expression did not correlate with severity of periodontal disease.

Effect of imidocarb and levamisole on the experimental infection of BALB/c mice by Leishmania (Leishmania) amazonensis.

The adverse effects from using currently available drugs for the treatment of leishmaniasis have motivated the search for new therapeutical agents. The aim of this work was to evaluate the effect of imidocarb and levamisole on the treatment of BALB/c mice experimentally infected by Leishmania (Leishmania) amazonensis. BALB/c mice were infected with 10(6) promastigotes of L. (L.) amazonensis (IFLA/BR/67/PH8) and, starting on day 51, mice were treated subcutaneously with imidocarb (IMD, 34 mg/kg), imidocarb plus levamisole (IMD+LVS, 34 and 12 mg/kg, respectively), only levamisole (LVS, 12 mg/kg) or without treatment (control). Lesion size and swelling were weekly monitored for 10 weeks after the beginning of the treatment. On day 121 post-infection, serum levels of specific IgG from infected mice were evaluated, as well as histopathological and morphometric alterations in the footpad, lymph nodes and spleen of these animals. The data obtained in this study demonstrated that, when compared to controls, mice treated with IMD had lower levels of IgG anti-L. (L.) amazonensis (34.45%), smaller vacuolar area in macrophages (3.75%), lower number of megakaryocytes in spleen (63.19%) and lower parasite burden in the footpad (30.2%). Thus, the evaluated parameters suggest the use of imidocarb as a potential drug in the treatment of tegumentary leishmaniasis.

Comparative effect of ion calcium and magnesium in the activation and infection of the murine macrophage by Leishmania major.

Amastigotes of Leishmania major have a great ability to evade destruction in host cells. This study investigated the activation in resident, inflammatory macrophages and J774 cells in vitro treated with lipopolysaccharide (LPS), soluble Leishmania antigen (SLA), calcium ionophore (CaI) and magnesium (Mg2+) alone or combined. An increase in nitric oxide (NO) production was observed in J774 or inflammatory macrophages treated with LPS alone or in combination with SLA and CaI. The same treatments did not affect the NO release by resident macrophages. There was no interference in uptake of L. major but CaI decreased intracellular proliferation of the parasite. This study demonstrated the importance of CaI in decreasing L. major proliferation inside murine macrophages while Mg2+ seemed to increase parasite proliferation. These finding may help to understand the events involved in host cells' clearance of this pathogen.

Comparative effect of ion calcium and magnesium in the activation and infection of the murine macrophage by Leishmania major

Amastigotes of Leishmania major have a great ability to evade destruction in host cells. This study investigated the activation in resident, inflammatory macrophages and J774 cells in vitro treated with lipopolysaccharide (LPS), soluble Leishmania antigen (SLA), calcium ionophore (CaI) and magnesium (Mg2+) alone or combined. An increase in nitric oxide (NO) production was observed in J774 or inflammatory macrophages treated with LPS alone or in combination with SLA and CaI. The same treatments did not affect the NO release by resident macrophages. There was no interference in uptake of L. major but CaI decreased intracellular proliferation of the parasite. This study demonstrated the importance of CaI in decreasing L. major proliferation inside murine macrophages while Mg2+ seemed to increase parasite proliferation. These finding may help to understand the events involved in host cells' clearance of this pathogen..