Glycobiology Advance Access published online on November 24, 2008
Glycobiology, doi:10.1093/glycob/cwn128
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Cooperation of specific ICAM-3 grabbing nonintegrin related 1 (SIGNR1) and complement receptor type 3 (CR3) in uptake of oligomannose-coated liposomes by macrophages
a Institute of Glycoscience
b Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259–1292, Japan
Corresponding to: Naoya Kojima, Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan, Phone: +81-463-58-1211, FAX: +81-463-50-2012, E-mail: naoyaki{at}keyaki.cc.u-tokai.ac.jp
Received on July 25, 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, and was 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: SIGNR1 / C-type lectin / oligomannose / CR3 / macrophage