Co-Investigator(Kenkyū-buntansha) |
MIYAKAWA Kazuhisa SCHOOL OF MEDICINE, Kumamoto University, ASSISTANT, 医学部, 助手 (00244111)
TAKAHASHI Kiyoshi SCHOOL OF MEDICINE, Kumamoto University, PROF., 医学部, 教授 (70045631)
SAKASHITA Naomi SCHOOL OF MEDICINE, Kumamoto University, ASSIS PROF., 医学部, 講師 (90284752)
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Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥6,000,000 (Direct Cost: ¥6,000,000)
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Research Abstract |
Macrophage scavenger receptor (MSR) is one of the major receptors of macrophages and play important roles in atherogenesis and host defense mechanisms. Monoclonal antibodies were generated by immunizing MSR-deficient mice with a recombinant protein of human type I MSR as immunogen. Five antibodies were confirmed to be specific for MSR by Western blot analysis. Immunohistochemically, all antibodies recognized tissue macrophages such as alveolar macrophages, Kupffer cells in the liver, red pulp macrophages in the spleen, sinus macrophages in lymph nodes, and interstitial macrophages in various organs. Perivascular macrophages in the brain (Mato cells) were also positive for these antibodies. Freshly isolated blood monocytes were negative ; however, they became positive for these antibodies after 1 day in culture. At 3 to 5 days in culture the reaction intensity became stronger along their differentiation towards macrophages. Dendritic cells such as interdigitating cells of lymphoid tissue
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s and epidermal Langerhans cells were invariably negative. In early atherosclerotic lesions, these antibodies recognized scattered macrophages in intima and foamy macrophages in the periphery of atheromatous cores. In various inflammatory conditions, these antibodies recognized infiltrated macrophages. Epithelioid cells and multinucleated giant cells in epithelioid granuloma of tuberculosis and sarcoidosis were also positive. Each antibody showed a unique reaction pattern against animal species. Especially, an antibody named SRA-E5 recognized MSR molecules of various animal species including monkeys, cows, horses, swine, beagles, cats, rabbits, guinea pigs, hamsters, rats, and mice. From these observations, these antibodies are considered to be useful not only for studying the role of MSRs but also for analyzing macrophage differentiation in human and animals. Through the evaluation of these antibodies at the 7th Workshop and Conference on Human Leucocyte Differentiation Antigens MSR has been assigned to be a new CD molecule, CD204. Less
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