| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
CD14^+CD16^+ monocytes have been implicated as a subpopulation of monocytes possessing an antigen presenting activity and known to be increased in number in inflammatory and infectious disorders such as tuberculosis, AIDS, and Kawasaki disease. To know the role of monocyte subpopulation in pathogenesis of sarcoidosis, the induction mechanism, characteristics and function of CD14^+CD16^+ cells were examined. Enough number of cells for function analysis was not harvested by freshly isolated mononuclear cells, using a magnet isolation system of monocytes and subsequent flowcytometry method. Therefore CD14^+CD16^+ cells were tried to be induced from monocytes by several kinds of cytokine combinations. Although MSCF/IL-4 or TGFβ, a previously reported induction factor of CD14^+CD16^+cells, did not induce a large number of the cells, MCSF/TGFβ or MSCF/IL10 strongly induced CD14^+CD16^+cells. To use teflon-coated dishes, instead of regular dishes, was also beneficial for the induction, probab
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ly because nonadherent cells were easily maintained. On the other hand, prostaglandin E2 significantly inhibited the induction by MSCF/IL-10. Among prostaglandin E_2 receptors, EP2 was associated with the induction. CD14^+CD16^+cells induced by the cytokines expressed CD80 but not CD1a. The expressions of chemokine receptors were CXCR^-, CCR4^<weak+>, CCR5^<++>, CCR6^<weak+>. In regard of the production of cytokines by M-CSF/IL-10-induced CD14^+CD16^+cells, MDP and p acnes induced high production of IL-1 and IL-6. To understand the involvement of Notch signals in the induction of CD14^+CD16^+cells, Notch ligand-coated dishes were used. The induction was significantly inhibited in jagged-1- or delta-1-coated dishes, suggesting that Notch signals was associated with CD14^+CD16^+ cells In regard of the experiment of epithelioid cell induction, monocytes cultured in teflon-coated dishes for long time did not show the features of epithelioid cells. Epithelioid cells were also not induced by vitamin D3 stimulation or in fibronectin-coated dishes. Less
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