Unique phagocytic properties of hemocytes of Pacific oyster Crassostrea gigas against yeast and yeast cell-wall derivatives.

For a marine bivalve mollusk such as Pacific oyster Crassostrea gigas, the elimination of foreign particles via hemocyte phagocytosis plays an important role in host defense mechanisms. The hemocytes of C. gigas have a high phagocytic ability for baker's yeast (Saccharomyces cerevisiae) and its cell-wall product zymosan. C. gigas hemocytes might phagocytose yeast cells after binding to polysaccharides on the cell-wall surface, but it is unknown how and what kinds of polysaccharide molecules are recognized. We conducted experiments to determine differences in the phagocytic ability of C. gigas hemocytes against heat-killed yeast (HK yeast), zymosan and zymocel, which are similarly sized and shaped but differ in the polysaccharide composition of their particle surface. We found that both the agranulocytes and granulocytes exerted strong phagocytic ability on all tested particles. The phagocytic index (PI) of granulocytes for zymosan was 9.4 ± 1.7, which significantly differed with that for HK yeast and zymocel (P < 0.05). To evaluate the PI for the three types of particles, and especially to understand the outcome of the much higher PI for zymosan, PI was gauged in increments of 5 (1-5, 6-10, 11-15, and ≥16), and the phagocytic frequencies were compared according to these increments. The results show that a markedly high PI of ≥16 was exhibited by 18.1% of granulocytes for zymosan, significantly higher than 1.7% and 3.9% shown for HK yeast and zymocel, respectively (P < 0.05). These findings indicate that the relatively high PI for zymosan could not be attributed to a situation wherein all phagocytic hemocytes shared a high mean PI, but rather to the ability of some hemocytes to phagocytose a larger portion of zymosan. To determine whether the phagocytosis of these respective particles depended on the recognition of specific polysaccharide receptors on the hemocyte surface, C. gigas hemocytes were pretreated with soluble α-mannan or ß-laminarin and then allowed to phagocytose the three types of the particles. The percentage of phagocytic cells of ß-laminarin-treated granulocytes decreased significantly for zymosan and zymocel, but not for yeast. These results suggest that C. gigas might possess at least two types of hemocytes, and that one type of the hemocytes (granulocytes) is more active for phagocytosis. The granulocytes were found to have multiple subtypes with different phagocytic abilities and multiple phagocytic receptors. Some of the granulocyte subtypes revealed a much stronger phagocytic ability, depending on the presence of ß-glucan receptors for phagocytosis.

Low-dose total-body carbon-ion irradiations induce early transcriptional alteration without late Alzheimer's disease-like pathogenesis and memory impairment in mice.

The cause and risk factors of Alzheimer's disease (AD) are largely unknown. Studies on possible radiation-induced AD-like pathogenesis and behavioral consequences are important because humans are exposed to ionizing radiation (IR) from various sources. It was reported that total-body irradiations (TBI) at 10 cGy of low linear energy transfer (LET) X-rays to mice triggered acute transcriptional alterations in genes associated with cognitive dysfunctions. However, it was unknown whether low doses of IR could induce AD-like changes late after exposure. We reported previously that 10 cGy X-rays induced early transcriptional response of several AD-related genes in hippocampi without late AD-like pathogenesis and memory impairment in mice. Here, further studies on two low doses (5 or 10 cGy) of high LET carbonion irradiations are reported. On expression of 84 AD-related genes in hippocampi, at 4 hr after TBI, 5 cGy induced a significant upregulation of three genes (Abca1, Casp3, and Chat) and 10 cGy led to a marked upregulation of one gene (Chat) and a downregulation of three genes (Apoe, Ctsd, and Il1α), and, at 1 year after TBI, one gene (Il1α) was significantly downregulated in 10 cGy-irradiated animals. Changes in spatial learning ability and memory and induction of AD-like pathogenesis were not detected by in vivo brain imaging for amyloid-ß peptide accumulation and by immunohistochemical staining of amyloid precursor protein, amyloid-ß protein, tau, and phosphorylated tau protein. These findings indicate that low doses of carbon-ion irradiations did not cause behavioral impairment or AD-like pathological change in mice.

Carbon ion beam is more effective to induce cell death in sphere-type A172 human glioblastoma cells compared with X-rays.

PURPOSE: To obtain human glioblastoma cells A172 expressing stem cell-related protein and comparison of radiosensitivity in these cells with X-rays and carbon beam. METHODS: Human monolayer-type A172 glioblastoma cells were maintained in normal medium with 10% bovine serum. In order to obtain sphere-type A172 cells the medium was replaced with serum-free medium supplemented with growth factors. Both types of A172 cells were irradiated with either X-rays or carbon ion beams and their radiosensitivity was evaluated. RESULTS: Serum-free medium induced expression of stem cell-related proteins in A172 cells along with the neurosphere-like appearance. These sphere-type cells were found resistant to both X-rays and carbon ion beams. Phosphorylation of histone H2A family member X persisted for a longer period in the cells exposed to carbon ion beams than in those exposed to X-rays and it disappeared quicker in the sphere type than in the monolayer type. Relative radioresistance of the sphere type cells was smaller for carbon ion beams than for X-rays. CONCLUSIONS: We demonstrated that glioblastoma A172 cells with induced stem cell-related proteins turned resistant to irradiation. Accelerated heavy ion particles may have advantage over X-rays in overcoming the tumor resistance due to cell stemness.

Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice.

The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with (11)C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aß) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aß, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aß, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice.