Effect of different fractions of Hibiscus rosa sinensis leaf extract on islets of Langerhans and antioxidant activity in non-obese diabetic (NOD) mouse

The present investigation was undertaken to study the effect of Hibiscus rosa sinensis leaf extract fractions on islets of Langerhans, total antioxidant activity in non-obese diabetic (NOD) mouse. Two sets of experiments were conducted. First experiment was designed to test the hypoglycemic properties of different isolated fractions. Five fractions were screened for hypoglycemic property. Fractions F3, F4 and F5 showed hypoglycemic in NOD mice. Second set of experiment was conducted to assess the effects of above fractions on the diameter of islets of Langerhans and on the â-cells number and total antioxidant capacity (TAC). All the fractions had a significant effect in the enhancement of diameter of islets of Langerhans and the â-cell number and antioxidant active (total antioxidant capacity) compared with control NOD mice

Studies on the Host-Parasite Relationship

Studies were conducted on the host-parasite relationship in Strongyloides ratti infections in rats. During initial infection, rats acquired a strong immunity against this parasite and 1. production and the expulsion of adult Infected rats were strongly resistant to reinfection and this immune response lasted for a period of three months, independent of the residual worm population. The immune response during initial infection caused a reduction in the size of adult worms after day 18 PI. Adult worms, which occupied the anterior half of the small intestine in the first 18 days, shifted to the posterior half before they were expelled.The Immune response affected the adult worm in the intestine during a primary infection, the migratory larvae in the lung during a secondary infection and the skin stage following multiple infections. In heavily infected rats, larvae disseminated and were detected in the brain tissue. A full infection with S. ratti induced complete resistance to reinfection, but adult worms were a major souroe of protective antigens, while migratory larvae did not stimulate an immune response against reinfection. "Normal" worms obtained on days 8-16 PI were able to continue their larval production when transferred to new, clean, rats; "damaged" worms obtained on days 18 - 25 PI were unable to do so. Worm damage during initial infection was irreversible. Short non-fertile worms found in rats early after challenge were able to resume their egg production and survive in new hosts. The possibility of adaptation was discussed. 22 day-old worms were examined under the electron microscope and were compared with 10 day-old worms. Damaged worms were smaller in size and showed vacuolation and tissue disorganisation, particularly the gut cells. Peculiar whorls were observed inside the gut lumen of damaged worms, and were suggested to be immune complexes. Precipitates were persistently observed surrounding the mouths of damaged worms. It was proposed that worm damage is instigated by immune complexes plugging the mouth and causing a state of starvation through inhibition of food intake. Worm expulsion was demonstrated to be an imrtunological event. Antibody mediated worm damaqe, in S. ratti, as an essential step in worm expulsion, was argued immume MINC alone, given on days 6 or 12 PI, were capable of inducing worm expulsion. Serum alone repeatedly induced auto-infection. A variety of factors were suggested to explain the action o f transferred antibodies. Co-operation between immune MLNC and serum in inducing worm expulsion was only evident when MLNC were given on day 12 PI. The tissue eosinophils Increased in the mucosa of Infected intestines immediately before worm expulsion, during initial and challenge infections. The percentage of degranulating mesenteric mast cells increased during the period of expulsion, and the introduction of histamine into the gut of infected rats caused a significant acceleration of worm damage and expulsion. Aspirin, a potent inhibitor of prostaglandins, delayed the action of expulsion for 5 days suggesting a possible role of prostaglandins in this process. Corticosteroid treatment caused the long persistanoe of S. ratti worms in the rats and indicated that worm damage was due to an immune response, and not to the worm's senescence. Levels of tissue eosinophils and degranulated mesenteric mast cells were also suppressed. No auto-infection was demonstrable when cortico steroid treatment commenced with the infection , but it was evident when the treatment started immediately prior to worm expulsion. Corticosteroids suppressed all manifestations of acquired immunity to reinfection. An attempt was made to render rats unresponsive to S. ratti infection by treating with corticosteroids at strategic periods during an initial infection

Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, eotaxin, exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1α, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1α, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung

Eosinophil granules function extracellularly as receptor-mediated secretory organelles

Intracellular granules in several types of leukocytes contain preformed proteins whose secretions contribute to immune and inflammatory functions of leukocytes, including eosinophils, cells notably associated with asthma, allergic inflammation, and helminthic infections. Cytokines and chemokines typically elicit extracellular secretion of granule proteins by engaging receptors expressed externally on the plasma membranes of cells, including eosinophils. Eosinophil granules, in addition to being intracellular organelles, are found as intact membrane-bound structures extracellularly in tissue sites of eosinophil-associated diseases. Neither the secretory capacities of cell-free eosinophil granules nor the presence of functional cytokine and chemokine receptors on membranes of leukocyte granules have been recognized. Here, we show that granules of human eosinophils express membrane receptors for a cytokine, IFN-γ, and G protein–coupled membrane receptors for a chemokine, eotaxin, and that these receptors function by activating signal-transducing pathways within granules to elicit secretion from within granules. Capacities of intracellular granule organelles to function autonomously outside of eosinophils as independent, ligand-responsive, secretion-competent structures constitute a novel postcytolytic mechanism for regulated secretion of eosinophil granule proteins that may contribute to eosinophil-mediated inflammation and immunomodulation

Transcriptional Changes in Schistosoma mansoni during Early Schistosomula Development and in the Presence of Erythrocytes

Schistosome blood flukes cause more mortality and morbidity than any other human worm infection, but current control methods primarily rely on a single drug. There is a desperate need for new approaches to control this parasite, including vaccines. People become infected when the free-swimming larva, the cercaria, enters through the skin and becomes the schistosomulum. Schistosomula are susceptible to immune responses during their first few days in the host before they become adult parasites. We characterised the genes that these newly transformed parasites switch on when they enter the host to identify molecules that are critical for survival in the human host. Some of these highly up-regulated genes can be targeted for future development of new vaccines and drugs

Dimerization of Translationally Controlled Tumor Protein Is Essential For Its Cytokine-Like Activity

BACKGROUND:Translationally Controlled Tumor Protein (TCTP) found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF). Human recombinant HRF (HrHRF) has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn). METHODS AND FINDINGS:We found that only NH(2)-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH(2)-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP) was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP). Allergenic activity of Del-N11TCTP prompted us to see whether the NH(2)-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. CONCLUSIONS:Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development

Mechanisms of eosinophil cytokine release

Human eosinophils have been demonstrated to contain a multitude of cytokines and chemokines that exist pre-formed within these cells. This content of pre-formed cytokines, with diverse potential biologic activities, provides eosinophils with capabilities distinct from most other leukocytes. The localization of pre-formed cytokines within eosinophils is both within specific granules and associated with substantial numbers of morphologically distinct cytoplasmic vesicles. Stimulation for release of specific cytokines, such as IL-4, leads to a regulated signal transduction cascade, which is dependent on the formation of leukotriene C4 within eosinophils where it acts as an intracrine mediator. IL-4 release occurs selectively and is by means of vesicular transport. The capabilities of eosinophils not only to rapidly release pre-formed cytokines but also to differentially regulate which cytokines are released endow eosinophils with distinct abilities in innate and acquired immunity