Immature dendritic cells reduce proinflammatory cytokine production by a coculture of macrophages and apoptotic cells in a cell-to-cell contact-dependent manner.
We have demonstrated that phagocytosis of late apoptotic cells by mouse macrophages leads to the production of proinflammatory cytokines, notably macrophage-inflammatory protein (MIP-2), and therefore, a yet-unknown mechanism(s) should keep our body free of inflammation. In this study, we examined the effect of the addition of immature dendritic cells (iDCs) to a coculture of macrophages and apoptotic cells on MIP-2 production and phagocytosis by macrophages. The addition of iDCs to the coculture reduced MIP-2 production significantly but unexpectedly enhanced the phagocytosis by macrophages. Further study revealed that the reduction of MIP-2 production was dependent on cell-to-cell contact partly involving the beta(2) integrin family Mac-1. In addition, anti-inflammatory cytokines, interleukin-10 and transforming growth factor-beta, were involved in the reduction of MIP-2 production, as antibodies against these cytokines recovered MIP-2 production. 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, suggesting that minute amounts of these anti-inflammatory cytokines were produced mainly by iDCs to block MIP-2 production in a cell-to-cell contact-dependent manner. Thus, this study reveals a new mechanism by which MIP-2 production by macrophages phagocytosing apoptotic cells is prevented.
Takahashi
Munehisa
M
Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan.
Kurosaka
Kahori
K
Kobayashi
Yoshiro
Y
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000096:biosynthesis; D013601:T-Lymphocytes; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D054426:Chemokine CXCL2; D016207:Cytokines; D015850:Interleukin-6; D015846:Monokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10