| Research Abstract |
Overexpression of Csk in a macrophage cell line, J774A.1, resulted in reduced productions of nitric oxide and monokines with reduced rates of phagocytosis and acetyl-LDL uptake. The transfectants also demonstrated enhanced production of PGEィイD22ィエD2. Somatic transgenesis with csk-gene into macrophages may be applicable to some diseases, in which macrophages may play important roles, such as hemophagocytic syndrome, demyelinating diseases, and atherosclerosis. Functional modulation of macrophages could be also achieved by inter-ferring macrophage migration inhibitory factor (MIF) with the anti-MIF antibody in rodents model of uveoretinitis, by either overexpressing or downregulating allograft inflammatory factor (AIF)-1 in atherosclerosis model mice, ApoEィイD1-/-ィエD1. Studies with MCP-1 transgenic mice revealed that MCP-1 plays critical roles in contact hypersensitivity responses by facilitating a migration of Langerhans cells in the skin and in endotoxemia via regulations of cytokine productions. Ath 7, a genetic locus which represent a resistance to atherosclerosis was shown to be expressed by macrophages. Bone marrow transplantation from resistant strains into ApoEィイD1-/-ィエD1 was shown to be a prominsing a strategy for a therapeutics.
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