ナマズ卵レクチンのクラスター形成と細胞内輸送

Rhamnose-binding lectins are widely found in fush eggs,and Silurus asotus lectin (SAL) isolated from catfish eggs having three carbohydrate recognition domains preferentially recognizes non-reducing end Galα-linked sugar chain.In the previous study,we revealed that SRL binds to globotriaosylceramide (Gb3) by the surface plasmon resonance analysis.However,its biological effect on cultured cells is still unclear.To investigate localization and trafficking of SAL in the renel adenocarcinoma ACHN cells,which express Gb3 on the cell surface,we prepared HiLyte Fluor 555-labeled SAL (HL-SAL).When ACHN cells were treated with HL-SAL at 4℃ for 5min, and at 37℃ for 24h,HL-SAL was distributed on the cell membrane and in the intracellular compartment,respectively.To trace the trafficking route of HL-SAL from cell surface to the intracellular compartment,the images of HL-SAL-treated live cells were obtained using confocal scanning microscopy.HL-SAL was clustered on ACHN cell surface,and furthermore,partially co-localised with transferrin in intracellular compartment.These results suggest that SAL induces alteration of Gb3 distribution on the membrane and migrates from the cell surface to the intracellular vesicles

A novel validated method for predicting the risk of re-hospitalization for worsening heart failure and the effectiveness of the diuretic upgrading therapy with tolvaptan.

Increased re-hospitalization due to acute decompensated heart failure (ADHF) is a modern issue in cardiology. The aim of this study was to investigate risk factors for re-hospitalization due to worsening heart failure, and the effect of tolvaptan (TLV) on decreasing the number of re-hospitalizations. This was a multicenter, retrospective study. The re-hospitalization factors for 1191 patients with ADHF were investigated; patients receiving continuous administration of TLV when they were discharged from the hospital (n = 194) were analyzed separately. Patients were classified into 5 risk groups based on their calculated Preventing Re-hospitalization with TOLvaptan (Pretol) score. The total number of patients re-hospitalized due to worsening heart failure up to one year after discharge from the hospital was 285 (23.9%). Age ≥80 years, duration since discharge from the hospital after previous heart failure 7.2 mg/dl, left ventricular ejection fraction (LVEF) 44.7 ml/m2, loop diuretic dose ≥20 mg/day, hematocrit <31.6%, and estimated glomerular filtration rate (eGFR) <50 ml/min/1.73m2 were independent risk factors for re-hospitalization for worsening heart failure. There was a significant reduction in the re-hospitalization rate among TLV treated patients in the Risk 3 group and above. In conclusions, age, duration since previous heart failure, diabetes mellitus, hemoglobin, uric acid, LVEF, LAVI, loop diuretic dose, hematocrit, and eGFR were all independent risk factors for re-hospitalization for worsening heart failure. Long-term administration of TLV significantly decreases the rate of re-hospitalization for worsening heart failure in patients with a Pretol score of 7

The involvement of central nervous system histamine receptors in psychological stress-induced exacerbation of allergic airway inflammation in mice

Background: Psychological stress is one of the major risk factors for asthma exacerbation. Although histamine in the brain acts as an excitatory and inhibitory neurotransmitter associated with psychological stress, the contribution of brain histamine to psychological stress-induced exacerbation of asthma remains unclear. The objective of this study was to investigate the role of histamine receptors in the CNS on stress induced asthma aggravation. Methods: We monitored the numbers of inflammatory cells and interleukin (IL)-13 levels in bronchoalveolar lavage fluid, airway responsiveness to inhaled methacholine, mucus secretion in airway epithelial cells, and antigen-specific IgE contents in sera in a murine model of stress-induced asthma treated with epinastine (an H1R antagonist), thioperamide (an H3/4R antagonist), or solvent. Results: All indicators of stress-induced asthma exacerbation were significantly reduced in stressed mice treated with epinastine compared with those treated with solvent, whereas treatment with thioperamide did not reduce the numbers of inflammatory cells in the stressed mice. Conclusions: These results suggest that H1R, but not H3/4R, may be involved in stress-induced asthma exacerbations in the central nervous system

CD8⁺ T Cells Mediate Female-Dominant IL-4 Production and Airway Inflammation in Allergic Asthma

<div><p>The prevalence and severity of bronchial asthma are higher in females than in males after puberty. Although antigen-specific CD8⁺ T cells play an important role in the development of asthma through their suppressive effect on cytokine production, the contribution of CD8⁺ T cells to sex differences in asthmatic responses remains unclear. In the present study, we investigated the sex-specific effect of CD8⁺ T cells in the suppression of asthma using an ovalbumin mouse model of asthma. The number of inflammatory cells in bronchoalveolar lavage (BAL) fluid, lung type 2 T-helper cytokine levels, and interleukin-4 (IL-4) production by bronchial lymph node cells were significantly higher in female wild-type (WT) mice compared with male mice, whereas no such sex differences were observed between male and female <i>cd8α</i>-disrupted mice. The adaptive transfer of male, but not female, CD8⁺ T cells reduced the number of inflammatory cells in the recovered BAL fluid of male recipient mice, while no such sex difference in the suppressive activity of CD8⁺ T cells was observed in female recipient mice. Male CD8⁺ T cells produced higher levels of IFN-γ than female CD8⁺ T cells did, and this trend was associated with reduced IL-4 production by male, but not female, CD4⁺ T cells. Interestingly, IFN-γ receptor expression on CD4⁺ T cells was significantly lower in female mice than in male mice. These results suggest that female-dominant asthmatic responses are orchestrated by the reduced production of IFN-γ by CD8⁺ T cells and the lower expression of IFN-γ receptor on CD4⁺ T cells in females compared with males.</p></div

Involvement of IFN-γ in sex differences in the inhibitory effect of BLN CD8⁺ T cells.

<p>(A) Intracellular cytokine expression by CD8⁺ T cells was analyzed using a flow cytometer. Data are shown as the mean ± SD of four mice. The expression of <i>Ifng</i> (B), <i>Gata3</i> and <i>Tbet</i> (C) in CD8⁺ T cells were measured by quantitative real-time RT-PCR. Data are shown as the mean ± SEM of four to eight mice. (D) Male CD4⁺ T cells (2 x 10⁵ cells/well), CD11c⁺ cells (2 x 10⁵ cells/well) and CD8⁺ T cells (0.66 x 10⁵ cells/well) were cultured with 50 μg/ml of OVA in presence of an anti- IFN-γ mAb (10 μg/ml) or control IgG for 72 h. The concentration of IL-4 in the culture supernatants was measured by ELISA. Data are shown as the mean ± SD of triplicate cultures. Experiment were repeated twice with similar results. *, P < 0.05; NS, not significant.</p