2005 Fiscal Year Final Research Report Summary
Responses in a coculture of macrophages, immature dendritic cells and apoptotic cells
| Project/Area Number |
16590068
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Toho University |
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Principal Investigator |
KOBAYASHI Yoshiro Toho University, Fac.of Sci, Professor, 理学部, 教授 (10134610)
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| Project Period (FY) |
2004 – 2005
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| Keywords | immature dendritic cells / apoptotic cells / macrophages / neutrophil / chemokine / class II |
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| Research Abstract |
We examined the effect of the addition of immature dendritic cells (iDCs) to a coculture of macrophages and apoptotic CTLL-2 cells on phagocytosis by macrophages and MIP-2 production. The more apoptotic cells macrophages phagocytosed, the more MIP-2 was produced by a coculture of macrophages and apoptotic cells. The addition of iDCs to the coculture, however, enhanced the phagocytosis by macrophages but reduced MIP-2 production. Further study revealed that the reduction of MIP-2 production was dependent on cell-to-cell contact partly involving β_2 integrin family Mac-1 as well as anti-inflammatory cytokine, IL-10 and TGF-β. Both cytokines were expressed by iDCs more significantly than macrophages at the mRNA levels, although they were hardly detected in the supernatant at the protein levels. On the other hand, while coculturing iDCs with apoptotic cells produced IL-6, the addition of macrophages to the coculture decreased phagocytosis by iDCs and IL-6 production, suggesting that reduction of IL-6 is caused by the decrease in phagocytosis. Thus this study reveals a new mechanism by which MIP-2 production by macrophages phagocytosing apoptotic cells is prevented. We then examined the effect of the addition of neutrophils to a cocultue of iDCs and apoptotic cells on class II expression and MIP-2 and KC production. The Class II expression and KC production but not MIP-2 production were significantly inhibited by the addition of neutrophils.
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