A NOVEL PLASMA FACTOR INITIATING COMPLEMENT ACTIVATION ON CETYLMANNOSIDE-MODIFIED LIPOSOMES IN HUMAN PLASMA

The possibility that the human complement (C) system plays a critical role in both destabilization and opsonization of the liposomes modifie d with cetylmannoside (Man-MLVs) was demonstrated in our previous in v itro study. In this study, our attention was focused on the underlying mechanism of activation of the C system by the Man-MLVs. It was found that the Man-MLVs had significant ability to activate the C system an d the activation proceeded through the Clq-dependent classical pathway . Pretreatment of human plasma with Man-MLVs at low temperature (4 deg rees C) diminished the ability of the C system to destabilize the homo logous liposomes without affecting the ability to lyse rabbit erythroc ytes. However, the C-dependent destabilization did not disappear by th e pretreatment with PC-MLVs. The results suggest that a plasma factor, which specifically adsorbs to Man-MLVs but not PC-MLVs, is essential for initiating the C activation. The plasma factor was obviously disti nguished from any known classical C pathway (CCP) activators, since th e adsorption of the plasma factor to Man-MLVs was not inhibited by tre atment with EGTA/Mg2+, soluble sugars (GlcNAc, ManNAc or D-mannose) or Con-A Sepharose. In addition, isolation of the plasma factor was atte mpted by the following procedure: PEG precipitation, DEAE Sepharose ch romatography and gel filtration chromatography. In a series of these i solations, the plasma factor was found to be a protein with higher mol ecular weight at least than 669000 Da. It was concluded that the activ ation of the human C system by the Man-MLVs proceeded through the CCP in the presence of a novel plasma factor. (C) 1998 Elsevier Science B. V. All rights reserved.