2010 Fiscal Year Final Research Report
Comparative immunological study on hematopoietic organ in dolphin
Project/Area Number |
20780145
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
General fisheries
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Research Institution | Nihon University |
Principal Investigator |
ITOU Takuya 日本大学, 生物資源科学部, 准教授 (20307820)
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Project Period (FY) |
2008 – 2010
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Keywords | イルカ / 造血 / モノクローナル抗体 / 好中球 / 好酸球 / 比較免疫学 / 造血細胞 |
Research Abstract |
The monoclonal antibody(DN1), which specifically reacts with the bottlenose dolphin neutrophils, was produced. The DN1 was useful for high-purity isolation of the dolphin granulocytes. The CD34, which specifically develops in the hematopoietic cells, were molecularly cloned in the bottlenose dolphin. The CD34 mRNA was strongly expressed in the bone marrow of the dolphin. Morphological observation has shown that the humerus is a source of hematopoietic tissue in dolphin.
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[Remarks] A new approach to bone biopsy in cetaceans
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[Remarks] In this issue of The Veterinary Journal, Itou et al.(2010) report a convenient method to sample bone marrow in cetaceans. This is a welcome addition to the veterinary armamentarium, because up to now veterinarians have been reluctant to carry out this procedure in cetaceans. Because the iliac crest and femur, the sampling sites used in terrestrial mammals, are absent in cetaceans, bone marrow is usually obtained from vertebrae, a site prone to iatrogenic damage. With the new proposed approach, practitioners have an additional diagnostic tool when confronted with the most common indications for bone marrow biopsy in cetaceans, such as anemia with no evidence of regeneration, regenerative anemia unresponsive to treatment, or, more rarely, an abnormal leukogram raising suspicions of leukemia/lymphoma.
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[Remarks] If biopsies of bone marrow are carried out more often, a better knowledge of the changes associated with physiological states such as aging will be gained. Bone marrow biopsy will also help to elucidate the etiology of new intriguing clinical conditions. For instance, anemia with various degrees of splenic and hepatic hemosiderosis is occasionally seen in cetaceans kept in aquaria. Some of these cases are probably due to chronic bacterial infections(D. Martineau, personal observation ; G. Bossart, personal communication). Other cases of anemia with hemosiderosis might be caused by chronic inflammatory states induced by bacteria newly described in cetaceans, such as Bartonella henselae and Brucella ceti, whose pathogenicity remains obscure ([Gonzalez-Barrientos et al., 2009] and [Maggi et al., 2008]). These intracellular bacteria are phylogenetically close and are both potential zoonotic agents(Wattam et al., 2009). They are known to infect bone marrow in terrestrial mammals and humans(Franco et al., 2007). In people, B. henselae is thought to infect and persist in erythrocytic progenitors within the bone marrow (Greub and Raoult, 2002 ; Florin et al., 2008). Whether Brucella spp. or Bartonella spp. infect the bone marrow has not been determined in cetaceans.
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[Remarks] Biopsy of bone marrow could also be useful in marine ecotoxicology to define the biological significance(e. g. toxicity) of environmental contaminants. Worldwide, free-ranging cetaceans are contaminated and variously intoxicated by polychlorinated biphenyls and polycyclic aromatic hydrocarbons, which are known immunosuppressive and/or carcinogenic compounds ([Martineau et al., 1987],[Martineau et al., 1988], [Marsili et al., 2001] and [Wells et al., 2005]). Bone marrow is one of the target organs for these contaminants ([Thurmond et al., 1999] and [Galvan et al., 2006]). New contaminants such as perfluorinated compounds, polybrominated diphenylether and their derivatives may also have an effect on the bone marrow (Yamamoto et al., 2006).
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[Remarks] Bone marrow stromal cells(BMSC) have been recently employed in the exciting new fields of cell and gene therapy. In human and veterinary medicine, BMSCs have been used as work horses for the expression of therapeutic proteins because they can be conveniently sampled in large numbers from the bone marrow of patients. For instance, autologous BMSCs genetically engineered to produce human, murine or canine erythropoietin have been sampled, engineered in vitro with the EPO gene from the corresponding species, and expanded in vitro. Subsequently, the EPO-engineered BMSCs have been implanted subcutaneously in a commercially available matrix in mice and dogs. The production and release of EPO has elevated hematocrit in these animals for weeks and even months. In addition, BMSC can differentiate in cardiomyocytes, myoblasts, osteoblasts, endothelial cells and other cell types. BMSCs are also able to induce neovascularisation. For these reasons, they have been used to repair necrotic cardiac muscle, and large bone defects in experimental 'regenerative' medicine(Fontaine et al., 2004 ; reviewed in Eliopoulos et al., 2008). Consequently, easy access to cetacean bone marrow(and consequently to BMSCs) could open the way to cell therapy in cetaceans.
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[Remarks] References Itou et al., 2010, Bone marrow biopsy from the flipper of a dolphin. The Veterinary Journal, 185(2010), pp. 216-217.他省略