IgE-mediated activation of NK cells through Fc gamma RIII

NK cells express Fc gamma RIII (CD16), which is responsible for IgG-dependent cell cytotoxicity and for production of several cytokines and chemokines. Whereas Fc gamma RIII on NK cells is composed of both Fc gamma RIII alpha and FcR gamma chains, that on mast cells is distinct from NK cells and made of Fc gamma RIII alpha, FcR beta, and FcR gamma. Mast cells show degranulation and release several mediators, which cause anaphylactic responses upon cross-linking of Fc gamma RIII as well as Fc epsilon RI with aggregated IgE. In this paper, we examined whether IgE activates NK cells through Fc gamma RIII on their cell surface. We found that NK cells produce several cytokines and chemokines related to an allergic reaction upon IgE stimulation. Furthermore, NK cells exhibited cytotoxicity against IgE-coated target cells in an Fc gamma RIII-dependent manner. These effects of IgE through Fc gamma RIII were not observed in NK cells from FcR gamma-deficient mice lacking Fc gamma RIII expression. Collectively, these results demonstrate that NK cells can be activated with IgE through Fc gamma RIII and exhibit both cytokine/chemokine production and Ab-dependent cell cytotoxicity. These data imply that not only mast cells but also NK cells may contribute to IgE-mediated allergic responses.     

Generation and analyses of R8L barttin knockin mouse

Barttin, a gene product of BSND, is one of four genes responsible for Bartter syndrome. Coexpression of barttin with ClC-K chloride channels dramatically induces the expression of ClC-K current via insertion of ClC-K-barttin complexes into plasma membranes. We previously showed that stably expressed R8L barttin, a disease-causing missense mutant, is retained in the endoplasmic reticulum (ER) of Madin-Darby canine kidney (MDCK) cells, with the barttin β-subunit remaining bound to ClC-K α-subunits (Hayama A, Rai T, Sasaki S, Uchida S. Histochem Cell Biol 119: 485-493, 2003). However, transient expression of R8L barttin in MDCK cells was reported to impair ClC-K channel function without affecting its subcellular localization. To investigate the pathogenesis in vivo, we generated a knockin mouse model of Bartter syndrome that carries the R8L mutation. These mice display disease-like phenotypes (hypokalemia, metabolic alkalosis, and decreased NaCl reabsorption in distal tubules) under a low-salt diet. Immunofluorescence and immunoelectron microscopy revealed that the plasma membrane localization of both R8L barttin and the ClC-K channel was impaired in these mice, and transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) as well as thiazide-sensitive chloride clearance were significantly reduced. This reduction in transepithelial chloride transport in tAL, which is totally dependent on ClC-K1/barttin, correlated well with the reduction in the amount of R8L barttin localized to plasma membranes. These results suggest that the major cause of Bartter syndrome type IV caused by R8L barttin mutation is its aberrant intracellular localization.     

Similarity in Nucleotide Sequence of the Gene Encoding Nontoxic Component of Botulinum Toxin Produced by Toxigenic Clostridium butyricum Strain BL6340 and Clostridium botulinum Type E Strain Mashike

The complete nucleotide and deduced amino acid sequence of the nontoxic component of botulinum type E progenitor toxin is determined in recombinant plasmid pU9BUH containing about 6.0 kb HindIII fragment obtained from chromosomal DNA of Clostridium butyricum strain BL6340. The open reading frame (ORF) of this nontoxic component gene is composed of 3,486 nucleotide bases (1,162 amino acid residues). The molecular weight calculated from deduced amino acid residues is estimated 13,6810.1. The present study revealed that 33 nucleotide bases of 3,486 are different in the nontoxic component gene between C.butyricum strain BL6340 and C. botulinum type E strain Mashike. This corresponds to the difference of 17 amino acid residues in these nontoxic component.     

Effects of Maitake (Grifola frondosa) glucan in HIV-infected patients

The effects of MD-Fraction, a β-glucan extracted from Maitake mushroom (Grifola frondosa), on the health status of individuals suffering from HIV infection were evaluated in a long-term trial. The HIV status of the 35 respondents who participated in the study was followed by monitoring CD4⁺ cell counts, viral load measure, symptoms of HIV infection, status of secondary disease, and sense of well-being. Twenty patients reported an increase in CD4⁺ cell counts to 1.4–1.8 times, and 8 patients reported a decrease to 0.8–0.5 times. Viral load was reported to increase in 9 patients and decrease in 10 patients. However, 85% of respondents reported an increased sense of well-being with regard to various symptoms and secondary diseases caused by HIV. These results suggest that Maitake D-Fraction had a positive impact in HIV patients.     

Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export

Mechanisms for exporting variably sized cargo from the endoplasmic reticulum (ER) using the same machinery remain poorly understood. COPII-coated vesicles, which transport secretory proteins from the ER to the Golgi apparatus, are typically 60–90 nm in diameter. However, collagen, which forms a trimeric structure that is too large to be accommodated by conventional transport vesicles, is also known to be secreted via a COPII-dependent process. In this paper, we show that Sec12, a guanine-nucleotide exchange factor for Sar1 guanosine triphosphatase, is concentrated at ER exit sites and that this concentration of Sec12 is specifically required for the secretion of collagen VII but not other proteins. Furthermore, Sec12 recruitment to ER exit sites is organized by its direct interaction with cTAGE5, a previously characterized collagen cargo receptor component, which functions together with TANGO1 at ER exit sites. These findings suggest that the export of large cargo requires high levels of guanosine triphosphate–bound Sar1 generated by Sec12 localized at ER exit sites.     

Induction of (6-4) photolyase gene transcription by blue light in Xenopus A6 cells

(6-4) photolyase repairs pyrimidine-pyrimidone (6-4) photoproducts generated in DNA upon UV light exposure. We studied the effects of blue light on the expression of this gene in Xenopus A6 cells. Exposure of the cells to blue light, but not red light, for 12 h resulted in more than 20-fold increase of the (6-4) photolyase mRNA. By contrast, levels of the other two photolyase mRNAs, i.e., those for CPD photolyase and cryptochrome DASH, did not change significantly. Oxygen radicals presumably generated within the cells upon exposure to blue light were not the cause of the induction, since addition of neither hydrogen peroxide nor a photosensitizer, phenol red, in the culture medium increased the (6-4) photolyase mRNA level. These results support the possibility that the expression of (6-4) photolyase may be regulated by a mechanism involving an as yet ill-defined blue light photoreceptor in the peripheral tissues of Xenopus.     

Improved walnut-feeding skills with experience in wood mice, <Emphasis Type="Italic">Apodemus speciosus</Emphasis>

The wood mouse Apodemus speciosus can consume the hard-walled walnut species Juglans ailanthifolia. The mice gnaw holes on two sides of the shell and then pick the meat from the holes. However, not all mice are able to eat these walnuts, because the shells are extremely hard and the process is labour-intensive. To consume all of the meat it is more efficient to eat from holes on the raphe than to attempt to eat from other parts of the shell. We examined the effect of experience on the walnut-feeding skills of mice in the field. Feeding behaviours were compared among mice from habitats with and without walnut trees. Mice from habitats with walnut trees tended to consume nuts more efficiently than mice from habitats without walnut trees. We also observed the feeding behaviour of mice in an experimental area into which walnuts were artificially placed over a period of one year. This manipulation increased the proportion of mice that were able to eat nuts frequently and efficiently. Therefore, the walnut-feeding skills of mice improved with experience. Because individual mice acquired efficient feeding during the 14-day period of walnut conditioning, trial-and-error learning may be an important mechanism contributing to this behaviour.