Complement-dependent cytotoxic activity of serum mannan-binding protein towards mammalian cells with surface-exposed high-mannose type glycans.
Serum mannan-binding protein (S-MBP), a lectin specific for mannose and N-acetylglucosamine, activates complement through the classical pathway. With the help of complement, S-MBP lyses red blood cells which have been coated with yeast mannan and kills bacteria which have N-acetylglucosamine and/or L-glycero-D-manno-heptose on their core oligosaccharide. In this study, we examined whether mammalian cells, on which S-MBP could bound, are killed by a complement-dependent mechanism. When baby hamster kidney (BHK) cells were treated with an alpha-mannosidase inhibitor, 1-deoxymannojirimycin (dMM), most of the cellular oligosaccharides were transformed from the complex-type to the high mannose-type. S-MBP bound to the dMM-treated BHK cells in the presence of Ca2+, and this binding was eliminated by mannose. When dMM-treated cells, labelled with 51Cr, were incubated with complement, radioactivity was released in a dose-dependent manner by S-MBP and complement. This release was not observed with heat-inactivated complement. These observations suggest that S-MBP is able, with the help of complement, to kill not only exogenous microorganisms but also mammalian cells which have high mannose-type oligosaccharides exposed on their surfaces.
Ohta
M
M
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Kawasaki
T
T
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002460:Cell Line; D037222:Collectins; D003167:Complement Activation / Q000187:drug effects*; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D037102:Lectins; D008351:Mannans; D008361:Mannosidases / Q000037:antagonists & inhibitors; D011134:Polysaccharides / Q000737:chemistry*; D043323:alpha-Mannosidase
D001798:Blood Proteins; D002352:Carrier Proteins; D037222:Collectins; D037102:Lectins; D008351:Mannans; D011134:Polysaccharides; D017485:1-Deoxynojirimycin; D008361:Mannosidases; D043323:alpha-Mannosidase