Journal of Biochemistry Advance Access originally published online on August 11, 2008
Journal of Biochemistry 2008 144(5):563-570; doi:10.1093/jb/mvn101
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© 2008 The Japanese Biochemical Society
Contribution of Complement Component C3 and Complement Receptor Type 3 to Carbohydrate-dependent Uptake of Oligomannose-coated Liposomes by Peritoneal Macrophages
1Department of Applied Biochemistry; 2Institute of Glycoscience, Tokai University, Hiratsuka, Kanagawa 259-1292; and 3National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan
*To whom correspondence should be addressed. Tel: +81-463-58-1211, ext. 4645, Fax: +81-463-50-2012, E-mail: naoyaki{at}keyaki.cc.u-tokai.ac.jp
Received July 17, 2008; Accepted August 7, 2008
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Abstract |
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Peritoneal macrophages (PEMs) preferentially and rapidly take up oligomannose-coated liposomes (OMLs) and subsequently mature to induce a Th-1 immune response following administration of OMLs into the peritoneal cavity. Here, we examine the contributions of complement component C3 and complement receptor type 3 (CR3) to carbohydrate-dependent uptake of OMLs by PEMs. Effective uptake of OMLs into PEMs in vitro was observed only in the presence of peritoneal fluid (PF), and OMLs incubated with PF were incorporated by PEMs in vitro in the absence of PF. These phenomena were inhibited by methyl-
-mannoside, N-acetylglucosamine or EDTA, but not by galactose. Pull-down analysis followed by peptide mass fingerprinting of PF-treated OMLs indicated that the OMLs were opsonized with complement fragment iC3b. In vivo uptake of OMLs by PEMs was inhibited by intraperitoneal injection of an antibody against CR3, a receptor for iC3b, and OML uptake by PEMs in the peritoneal cavity was not observed in C3-deficient mice. Thus, our results indicate that OMLs are opsonized with iC3b in a mannose-dependent manner in the peritoneal cavity and then incorporated into PEMs via CR3.
Key Words: complement C3, CR3, C-type lectin, macrophage, oligomannose
Abbreviations: APC, antigen-presenting cell; OML, oligomannose-coated liposome; PEC, peritoneal cell; PEM, peritoneal macrophage; PF, peritoneal fluid
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