Modified low density lipoproteins differentially bind and activate the C1 complex of complement

摘要: Several studies suggest that complement plays an important role in atherogenesis. To further investigate this question, we have studied the ability of native and modified forms low density lipoprotein (LDL) to bind activate C1, complex triggers classical pathway complement. For purpose, LDL was both obtained commercially purified according established procedure, oxidized (oxLDL) enzymatically (E-LDL) derivatives were generated from each preparation. Whereas unmodified oxLDL samples did not C1 presence excess inhibitor, E-LDL by sequential treatment with a protease then cholesterol esterase triggered efficient activation under these conditions, levels approximately 60% upon incubation 1 microM for 90 min at 37 degrees C. In agreement findings, as shown surface plasmon resonance spectroscopy (SPR), C1q recognition subunit showed no interaction but bound high affinity (K(D)=58-75 nM). More unexpectedly, although they trigger direct activation, also efficiently recognized C1q. derivative commercial activated significant extent ( 30%) C-reactive protein (CRP), much lower (<10%) using LDL. As measured SPR, CRP equally well These data provide first experimental evidence conditions close physiological situation, suggesting may be crucial factor pathogenesis atherosclerosis. contrast, it appears unlikely significantly activates directly or CRP-dependent manner vivo.