Metabolic properties of normal and mutant mannan-binding proteins in mouseplasma

Human mannan-binding protein (MBP) is a serum lectin involved in innate imm unity. MBP activates the complement pathway through its interaction with ma nnose-rich carbohydrates on various microorganisms and a common opsonic def ect has been shown to be associated with a low serum concentration of MBP. This low serum concentration is closely associated with a single base mutat ion in codon 52, 54 or 57 of the human MBP gene, which results in a change of Arg52 to Cys, Gly54 to Asp, or Gly57 to Gln, respectively, in the collag en-like region of the molecule and prevents the formation of higher oligome rs. However, the mechanism underlying the low serum concentration in such p atients is completely unknown. The levels of protein synthesis and secretio n of the normal and mutant MBPs seem to be similar according to our previou s in vitro results. In this study, we examined the plasma clearance of the normal and mutant human (Gly54Asp) MBPs in mice, and found that the half-li fe of the mutant MBP is about half that of the normal MEP, explaining in pa rt the difference in the plasma levels between the two types of MBP. (C) 19 99 Academic Press.