The effect of conglutinin on production of reactive oxygen species in bovine granulocytes

Conglutinin is a high molecular-weight lectin originally detected in bovine serum. It belongs to the family of collectins that bind sugar residues in a Ca(2+)-dependent manner and are effector molecules in innate immunity. Conglutinin appears to play an important role in immune defense mechanisms, showing antiviral and antibacterial activities when tested in vivo and in vitro. The present study evaluated the effect of conglutinin on the respiratory bursts in bovine peripheral phagocytes. Using nitroblue tetrazolium and hydrogen peroxide assays, we showed that sugar ligand-bound conglutinin stimulated the production of superoxide and H2O2 in granulocytes whereas the non-sugar-bound form of conglutinin inhibited these processes. These results indicate that both forms of conglutinin are able to interact with surface leukocyte receptors but have opposite effects on phagocytic activity. Our findings suggest that conglutinin bound to sugar residues on microbial surfaces can induce oxygen burst in phagocytes, and thereby mediates the elimination of pathogens and prevents the spread of infection.

Immunomodulatory effects of betulinic acid from the bark of white birch on mice

The objective of this study was to explore the immunomodulatory effects of betulinic acid (BA) extracted from the bark of white birch on mice. Female mice were orally administered BA for 14 days in doses of 0, 0.25, 0.5, and 1 mg/kg body weight. We found that BA significantly enhanced the thymus and spleen indices, and stimulated lymphocyte proliferation induced by Concanavalin A and lipopolysaccharide as shown by MTT assay. Flow cytometry revealed that BA increased the percentage of CD4+ cells in thymus as well as the percentage of CD19+ and the ratios of CD4+/CD8+ in spleen. BA increased the number of plaque-forming cell and macrophage phagocytic activity as indicated by a neutral red dye uptake assay, and the peritoneal macrophages levels of TNF-alpha were also increased. In contrast, serum levels of IgG and IgM and serum concentrations of IL-2 and IL-6 were significantly decreased in BA-treated mice compared to the control as assayed by haemagglutination tests and ELISA, respectively. Taken together, these results suggest that BA enhances mouse cellular immunity, humoral immunity, and activity of macrophages. Thus, BA is a potential immune stimulator and may strengthen the immune response of its host.

Revisiting steroid treatment for septic shock: molecular actions and clinical effects - a review

Corticosteroids are widely used to treat a diversity of pathological conditions including allergic, autoimmune and some infectious diseases. These drugs have complex mechanisms of action involving both genomic and non-genomic mechanisms and interfere with different signal transduction pathways in the cell. The use of corticosteroids to treat critically ill patients with acute respiratory distress syndrome and severe infections, such as sepsis and pneumonia, is still a matter of intense debate in the scientific and medical community with evidence both for and against its use in these patients. Here, we review the basic molecular mechanisms important for corticosteroid action as well as current evidence for their use, or not, in septic patients. We also present an analysis of the reasons why this is still such a controversial point in the literature.

Prodigiosins: a novel family of immunosuppressants with anti-cancer activity.

Prodigiosins (PrGs) are a family of promising therapeutic molecules, isolated mostly from Gram-negative bacteria and characterized by a common pyrryldipyrrylmethene structure with varying side chains. They show a broad spectrum of activities such as anti-microbial, anti-malarial, anti-cancer and immunosuppressive. PrGs are attracting increasing attention due to the ongoing research for less toxic, but effective agents for cancer chemotherapy and immunosuppression for preventing allograft rejection and autoimmunity. Different analogues have been synthesized and evaluated. This review discusses the immunosuppressive and anti-cancer activities of this class of compounds, as both involve inhibition of cell proliferation. The main focus is on the in vitro and in vivo immunosuppressive activity of the different PrGs and the mechanisms involved. PrGs primarily target the T cells, though some effects are observed on other cell types also. Unlike the well-known immunosuppressant cyclosporin A, PrGs do not inhibit the secretion of IL-2 but inhibit the mitogenic signaling from IL-2, suggesting a different mechanism of action. Janus tyrosine kinase 3 (Jak3) that associates with IL-2R upon activation is considered as the molecular target for PrGs. Its restricted expression makes Jak3 as an attractive target for immunosuppressive therapy. However, the available literature suggests that some other pathways are also influenced by the PrGs. These may be important for the anti-cancer activity, as well as immunosuppressive action. Therefore, PrGs appear to be potential candidates for pharmaceutical development as immunosuppressants and also as anti-cancer agents.

Immunomodulatory role of arabinosylated lipoarabinomannan on Leishmania donovani infected murine macrophages.

Arabinosylated lipoarabinomannan (Ara-LAM), a surface glycolipid antigen isolated from avirulent Mycobacterium smegmatis is involved in modulation of host cell signaling. In this study, we investigated Ara-LAM-mediated modulation of impaired immune responses during visceral leishmaniasis caused by protozoan parasite Leishmania donovani. Ara-LAM treatment at dose of 3 microg/ml in L. donovani infected murine peritoneal macrophages as well as J774A.1 macrophage cell line exhibited a distinct up-regulation of pro-inflammatory cytokines like TNF-alpha and IL-12 both at the protein and transcriptional level. In addition, generation of nitric oxide and iNOS expression were also observed. The present study showed that Ara-LAM was significantly effective in elimination of L. donovani parasites from both peritoneal as well as J774A.1 macrophages. Thus, it could be utilized as an immunomodulatory agent in prevention of leishmanial pathogenesis.

Activation of Intrarenal Complement System in Mouse Model for Chronic Cyclosporine Nephrotoxicity

PURPOSE: Local activation of the complement system plays a role in target organ damage. The aim of our study was to investigate the influence of cyclosporine (CsA)- induced renal injury on the complement system in the kidney. MATERIALS AND METHODS: Mice fed a low salt (0.01%) diet were treated with vehicle (VH, olive oil, 1mL/kg/day) or CsA (30mg/kg/day) for one or four weeks. Induction of chronic CsA nephrotoxicity was evaluated with renal function and histomorphology. Activation of the complement system was assessed through analysis of the expression of C3, C4d, and membrane attack complex (MAC), and the regulatory proteins, CD46 and CD55. CsA treatment induced renal dysfunction and typical morphology (tubulointerstitial inflammation and fibrosis) at four weeks. RESULTS: CsA-induced renal injury was associated with increased the expression of C3, C4d, and MAC (C9 and upregulation of complement regulatory proteins (CD 46 and CD55). Immunohistochemistry revealed that the activated complement components were mainly confined to the injured tubulointerstitium. CONCLUSION: CsA-induced renal injury is associated with activation of the intrarenal complement system.

Influence of jasmonic acid as potential activator of induced resistance against Karnal bunt in developing spikes of wheat.

Induction of defense response against Karnal bunt (KB)by suppressing the pathogenesis was observed upon exogenous application of jasmonic acid (JA)as evident from decrease in the coefficient of infection and overall response value in both susceptible and resistant varieties of wheat. The ultra-structural changes during disease progression showed the signs of programmed cell death (PCD). However, JA strengthened the defense barrier by enhancing the lignifications of cell walls as observed in spikes of both varieties by histochemical analysis. Compared to the plants inoculated with pathogen alone, plants of resistant line (RJP) first treated with JA followed by inoculation with pathogen showed more lignifications and extracellular deposition of other metabolites on cells, which is supposed to prevent mycelial invasions. Contrary to this, susceptible (SJP)lines also showed lignifications but the invasion was more compared to resistant line.Induction of protease activity was higher in resistant variety than its corresponding susceptible variety. The protease activity induced during the colonization of the pathogen and its proliferation inside the host system gets inhibited by JA treatment as demonstrated by the quantitative and in-gel protease assay. The results indicate the role of JA signalling in inhibiting the proteases due to expression of certain protease inhibitor genes. SDS-PAGE analysis shows differential gene expression through induction and/or suppression of different proteins in wheat spikes of resistant and susceptible varieties under the influence of JA. Thus, exogenously applied JA provides the conditioning effect prior to the challenge of infection and induces defense against KB probably by maintaining a critical balance between proteases and protease inhibitors and/or coordinating induction of different families of new proteins.

Immunostimulatory effect of Tinospora cordifolia Miers leaf extract in Oreochromis mossambicus.

Immunostimulatory effect of leaf extract of T. cordifolia on (i) specific immunity (antibody response), (ii) non-specific immunity (neutrophil activity) and (iii) disease resistance against Aeromonas hydrophila was investigated in O. mossambicus. Ethanol and petroleum ether extracts of the leaves were used. Both ethanol and petroleum ether extracts administered at doses of 0.8, 8 or 80 mg/kg body weight, prolonged the peak primary antibody titres upto one to three weeks. Ethanol extract at the dose of 8 mg/kg and petroleum ether extract at the doses of 0.8 or 8 mg/kg enhanced the secondary antibody response. All the doses of ethanol extract significantly enhanced neutrophil activity. Fish injected with petroleum ether or ethanol extract at a dose of 8 mg/kg were protected against experimental infection with virulent A. hydrophila. The results indicates the potential of T. cordifolia leaf extracts for use as an immunoprophylactic to prevent diseases in finfish aquaculture.

Immunomodulation by 'Immuplus (AquaImmu)' in giant freshwater prawn, Macrobrachium rosenbergii (De Man).

ImmuPlus, a polyherbal commercial formulation was used to modulate the immune system of commercially important giant freshwater prawn M. rosenbergii. The prawns were fed with basal diet supplemented with ImmuPlus at 1g/kg feed for 4 weeks. Results showed that the phenoloxidase activity (PO), haemagglutination and lysozyme activities were significantly elevated in ImmuPlus-fed prawn up to 3 weeks of feeding and declined after 4 weeks of feeding. The total protein level in ImmuPlus-fed prawn raised up to 2nd week of feeding. Incorporation of ImmuPlus at the rate of 1g/kg feed in the diet of prawn for 3 weeks may be beneficial in raising the immune status of prawn.

Avirulent mutants of Macrophomina phaseolina and Aspergillus fumigatus initiate infection in Phaseolus mungo in the presence of phaseolinone; levamisole gives protection.

To evaluate the role of phaseolinone, a phytotoxin produced by Macrophomina phaseolina, in disease initiation, three nontoxigenic avirulent mutants of the fungus were generated by UV-mutagenesis. Two of them were able to initiate infection in germinating Phaseolus mungo seeds only in the presence of phaseolinone. The minimum dose of phaseoli-none required for infection in 30% seedlings was 2 5 mg/ml. A human pathogen, Aspergillus fumigatus was also able to infect germinating seeds of P. mungo in the presence of 5 mg/ml concentration of phaseolinone. Phaseolinone seemed to facilitate infection by A. fumigatus, which is not normally phytopathogenic, by reducing the immunity of germinating seedlings in a nonspecific way. Levamisole, a non-specific immunopotentiator gave protection against infection induced by A. fumigatus at an optimum dose of 50 mg/ml. Sodium malonate prevented the effects of levamisole.

Resistência microbiana aos antibióticos / Microbial resistance to antibiotics

O presente trabalho objetiva demonstrar, através da revista da literatura, a importância clínica do aumento da resistência microbiana aos antibióticos, quais as suas consequências em relaçäo ao controle das doenças infecciosas, como se dá a aquisiçäo de resistência pelos microorganismos e algumas formas eficientes de tentar diminuir os índices alarmantes deste problema, que surgiu praticamente junto com o advento dos antibióticos, a partir de década de 40

Inducción de resistencia contra Toxoplasma gondii en ratones NIH tratados con concanavalina A / Induction of resistence against Toxoplasma gondii in NIH mice treated with concanavalin A

Se evaluó el efecto de la administración de concanavalina A (Con A) en ratones expuestos a Toxoplasma gondii. Cuarenta y ocho ratones, cepa NIH (hembras de 22 a 24 g), libres de parásitositos, fueron distribuidos al azar en ocho grupos (A1, A2, B1, B2, C1, C2, D1, D2) de seis animales cada uno. Estos, fueron inoculados por vía intraperitoneal (i.p.) de la siguiente manera: los de los grupos A, B y C recibieron 10, 20 y 40 µg de Con A, respectivamente, mientras que los del grupo D recibieron 0.1 ml de solución salina fisiológica. Todos los ratones fueron confrontados por vía i.p. con 2 LD DE T. gondii, cepa RH. Los de los grupos A1, B1, C1 y D1 fueron expuestos al protozoario dos días después del tratamiento; mientras que los de los grupos A2, B2, C2 y D2, siete días después de éste. Los porcentajes de animales sobrevivientes obtenidos 15 días después de la infección, fueron 16.66, 16.66, 0, 0, 33.33, 50, 16.66 y 0 para los grupos A1, B1, C1, D1, A2, B2, C2 y D2, respectivamente. Para corroborar los resultados obtenidos en los últimos cuatro grupos, se repitió el experimento, después del cual se observaron consecuencias similares, excepto que en el grupo tratado con 40 µg de Con A, se obtuvo una sobrevivencia del 33.33 por ciento. Los datos obtenidos indican que la inyección i.p. de Con A en ratones NIH genera una protección parcial insepecífica contra T. gondii cepa RH, la cual aumenta si se aplican 20 µg del mitógeno siete días antes de la confrontación

Flora autóctona intestinal: Revisión Bibliográfica / Autochthonous intestinal flora: bibliographic review

Se revisan diversos aspectos sobre la flora autóctona intestinal en el niño sano y en el enfermo. Su asociación con la antibioticoterapia y la dieta, los efectos metabólicos sobre la flora intestinal, su manipulación y su relación con el sistema inmunológico

Modulatory effects of metanil yellow on immunity in rodents.

Pathomorphological and immunological studies were carried out on rodents following oral administration of 0, 0.1, 0.25 and 0.5% (w/w) metanil yellow, mixed in diet, for 30 days. No significant change in hematologic parameters and histologic architecture of liver, kidney, mesenteric lymph node, thymus and urinary bladder was observed except for mild desquamation of intestinal villi and moderate changes in Peyer's patches of small intestine with higher doses. Among immunological parameters, significant enhancement in the primary humoral immune response (anti-SRBC IgM plaque forming cells of spleen) was observed with the lowest dose of metanil yellow while higher doses produced opposing effects. An elevated cutaneous delayed type hypersensitivity (DTH) reaction to SRBC was seen in 0.1% metanil yellow treated animals but higher doses did not influence the reaction. The treatment also caused changes in functional capabilities of macrophages. Although these immune alterations could hardly influence the local immunity of gut, as measured by the capacity of animals to cause rejection of Nippostrongylus brasiliensis parasite, the potential to modulate the immunity in general by metanil yellow however assumes considerable biological significance.

Evidence for the participation of mast cells in the innate resistance of mice to Schistosoma mansoni: effects on in vivo treatment with the ionophore 48-80

1. Evidence is presented for the participation of mast cells in the resistance of mice to infection by Schistosoma mansoni. 2. Intravenous injection of 1 microng/g body of the ionophore 48-80, a potent mast cell degranulator, significantly reduced (42-62%) the histamine content of the ear tisse of normal mice and either inceased or decreased resistance to parasite penetration and infection depending on whether the injection of the ionophore was i min or 2 days before cervarial penetration. 3. When 48-80 was injected 5 min before the benning of cercarial penetration, the number of parasites recovered from ear tissue 2 days later or from the portal system 30 days later was significantly reduced (39-71% and 27-40%, respectively) in relation to untreated controls. This resistance caused by 48-80 was blocked when mice were simultaneously treated with cyproheptadine, an antagonist of vasoactive amines. 4. In contrast, when 48-80 was administered 2 days before the beginning of cercarial penetration, the number of parasites retrieved from ear tissue 2 days later or from the portal system 30 days later was 32-64% and 28-30% larger, respectively, in relation to untreated controls. 5. These findings indicate that the local inflammatory reaction mediated by mast cells is important in the resistance of mice to infection with S. mansoni

Efecto de los corticosteroides sobre la adaptación natural de la rata blanca al Toxoplasma / Effect of corticosteroids on the natural adaptation to Toxoplasma

Ratas adultas normales (Sprague-Dowley) que son naturalmente resistentes a la infección con Toxoplasma gondii, fueron tratadas semanalmente con 10 ó 20 mg de cortisona por 100 grs de peso corporal, previa infección con diferentes concentraciones de Toxoplasma. Grupos de animales fueron infectados con 10**5, 10**6 y 10**7 taquizoitos del parásito. Mientras que los animales testigo inoculados con el Toxoplasma sobrevivieron los 90 días que duró el experimento, aquellas ratas tratadas con 20 mg de cortisona x c/100 g de peso murieron con una toxoplasmosis aguda, independientemente del inóculo empleado. Las ratas infectadas con 10**6 y 10**7 toxoplasmas y tratadas con 10 mg de acetado de cortisona por cada 100 g de peso, también desarrollaron la enfermedad aguda entre 8 y 74 días después de la infección. Este efecto aparentemente inmunosupresor se observó en ratas de 87 + ou - 6 grs no en ratas de 150 g. Estos experimentos indican que los corticosteroides pueden producir una disminución en la resistencia natural contra el Toxoplasma, aspecto que se discute en comparación con infecciones diseminadas en humanos debido al tratamiento con estas drogas