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Glycobiology Advance Access originally published online on November 24, 2008
Glycobiology 2009 19(3):258-266; doi:10.1093/glycob/cwn128
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Cooperation of specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) and complement receptor type 3 (CR3) in the uptake of oligomannose-coated liposomes by macrophages

Hideaki Takagi2,3, Maki Numazaki3, Toshimitsu Kajiwara2, Yu Abe3, Mariko Ishii3, Chiaki Kato2 and Naoya Kojima1,2,3

2 Institute of Glycoscience
3 Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan

1 To whom correspondence should be addressed: Tel: +81-463-58-1211; Fax: +81-463-50-2012; e-mail: naoyaki{at}keyaki.cc.u-tokai.ac.jp

Received on July 25, 2008; revised on November 12, 2008; accepted on November 15, 2008

Resident peritoneal macrophages (PEMs) express SIGNR1 on the cell surface as a major mannose receptor. These cells also ingest oligomannose-coated liposomes (OMLs) in an oligomannose-dependent manner following intraperitoneal administration. Therefore, the current study was conducted to investigate the possible role of SIGNR1 in capture of OMLs. Transient expression of several SIGN-related lectins potentially expressed on PEMs in CHO cells revealed that only SIGNR1 contributed to capture of OMLs. When SIGNR1 was introduced into mouse macrophage-like RAW264.7 cells, SIGNR1-expressing RAW (RAW-SIGNR1) cells recognized OMLs under serum-free conditions. OML recognition by RAW-SIGNR1 cells as well as that by PEMs was partially inhibited by an anti-SIGNR1 antibody (ER-TR9) and by mannan, and completely inhibited by EDTA. Interestingly, OML recognition by RAW-SIGNR1 cells was accelerated in the presence of serum, partially inhibited by an anti-complement receptor 3 (CR3) antibody (M1/70), and almost completely inhibited by a combination of ER-TR9 and M1/70. Complete inhibition of OML ingestion by the combination of ER-TR9 and M1/70 was also observed under serum-free conditions, suggesting that SIGNR1 and CR3 cooperate in an additive way in capture of OMLs by macrophage-like RAW cells. Administration of ER-TR9 or M1/70 into the peritoneal cavity led to a significant decrease of OML uptake by PEMs. Therefore, SIGNR1 expressed on macrophages acts as a receptor for recognition of OMLs under physiological conditions.

Key words: complement receptor 3 / C-type lectin / macrophage / oligomannose / phagocytosis / SIGNR1


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