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Enzymatically modified low-density lipoprotein is recognized by c1q and activates the classical complement pathway.

Arlaud GJ, Biro A, Ling WL - J Lipids (2011)

Bottom Line: To further investigate this question, we have studied the ability of native and modified forms of LDL to bind and activate C1, the complex protease that triggers the classical pathway of complement.Further investigations revealed that C1q recognizes a lipid component of E-LDL.Several approaches, including reconstitution of model lipid vesicles, cosedimentation, and electron microscopy analyses, provided evidence that C1 binding to E-LDL particles is mediated by the C1q globular domain, which senses unesterified fatty acids generated by cholesterol esterase.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.

ABSTRACT
Several studies suggest that the complement system is involved in atherogenesis. To further investigate this question, we have studied the ability of native and modified forms of LDL to bind and activate C1, the complex protease that triggers the classical pathway of complement. Unlike native LDL, oxidized (oxLDL) and enzymatically modified (E-LDL) derivatives were both recognized by the C1q subunit of C1, but only E-LDL particles, obtained by sequential treatment with a protease and then with cholesterol esterase, had the ability to trigger C1 activation. Further investigations revealed that C1q recognizes a lipid component of E-LDL. Several approaches, including reconstitution of model lipid vesicles, cosedimentation, and electron microscopy analyses, provided evidence that C1 binding to E-LDL particles is mediated by the C1q globular domain, which senses unesterified fatty acids generated by cholesterol esterase. The potential implications of these findings in atherogenesis are discussed.

No MeSH data available.


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Analysis by surface plasmon resonance spectroscopy of the interaction between C1q and immobilized E-LDL. The E-LDL derivative (14,000 resonance units) was immobilized chemically on the surface of a CM5 sensor chip (GE Healthcare) and allowed to bind to increasing concentrations of soluble C1q (100–600 nM). The KD value was determined from the ratio of the dissociation and association rate constants (koff/kon) (taken from [14], with permission).
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fig1: Analysis by surface plasmon resonance spectroscopy of the interaction between C1q and immobilized E-LDL. The E-LDL derivative (14,000 resonance units) was immobilized chemically on the surface of a CM5 sensor chip (GE Healthcare) and allowed to bind to increasing concentrations of soluble C1q (100–600 nM). The KD value was determined from the ratio of the dissociation and association rate constants (koff/kon) (taken from [14], with permission).

Mentions: The ability of C1q, the recognition unit of C1, to bind native LDL and its modified forms was investigated by surface plasmon resonance spectroscopy, using the lipoproteins as immobilized ligands and C1q as the soluble analyte. C1q did not show significant binding to native LDL but readily bound to both oxLDL and E-LDL. By recording binding curves at varying C1q concentrations, as illustrated in Figure 1 for E-LDL, the dissociation constants (KD) were determined. E-LDL and oxLDL each yielded values in the nanomolar range (23–75 nM), indicating that C1q binds both derivatives with high affinity [14].


Enzymatically modified low-density lipoprotein is recognized by c1q and activates the classical complement pathway.

Arlaud GJ, Biro A, Ling WL - J Lipids (2011)

Analysis by surface plasmon resonance spectroscopy of the interaction between C1q and immobilized E-LDL. The E-LDL derivative (14,000 resonance units) was immobilized chemically on the surface of a CM5 sensor chip (GE Healthcare) and allowed to bind to increasing concentrations of soluble C1q (100–600 nM). The KD value was determined from the ratio of the dissociation and association rate constants (koff/kon) (taken from [14], with permission).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066639&req=5

fig1: Analysis by surface plasmon resonance spectroscopy of the interaction between C1q and immobilized E-LDL. The E-LDL derivative (14,000 resonance units) was immobilized chemically on the surface of a CM5 sensor chip (GE Healthcare) and allowed to bind to increasing concentrations of soluble C1q (100–600 nM). The KD value was determined from the ratio of the dissociation and association rate constants (koff/kon) (taken from [14], with permission).
Mentions: The ability of C1q, the recognition unit of C1, to bind native LDL and its modified forms was investigated by surface plasmon resonance spectroscopy, using the lipoproteins as immobilized ligands and C1q as the soluble analyte. C1q did not show significant binding to native LDL but readily bound to both oxLDL and E-LDL. By recording binding curves at varying C1q concentrations, as illustrated in Figure 1 for E-LDL, the dissociation constants (KD) were determined. E-LDL and oxLDL each yielded values in the nanomolar range (23–75 nM), indicating that C1q binds both derivatives with high affinity [14].

Bottom Line: To further investigate this question, we have studied the ability of native and modified forms of LDL to bind and activate C1, the complex protease that triggers the classical pathway of complement.Further investigations revealed that C1q recognizes a lipid component of E-LDL.Several approaches, including reconstitution of model lipid vesicles, cosedimentation, and electron microscopy analyses, provided evidence that C1 binding to E-LDL particles is mediated by the C1q globular domain, which senses unesterified fatty acids generated by cholesterol esterase.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.

ABSTRACT
Several studies suggest that the complement system is involved in atherogenesis. To further investigate this question, we have studied the ability of native and modified forms of LDL to bind and activate C1, the complex protease that triggers the classical pathway of complement. Unlike native LDL, oxidized (oxLDL) and enzymatically modified (E-LDL) derivatives were both recognized by the C1q subunit of C1, but only E-LDL particles, obtained by sequential treatment with a protease and then with cholesterol esterase, had the ability to trigger C1 activation. Further investigations revealed that C1q recognizes a lipid component of E-LDL. Several approaches, including reconstitution of model lipid vesicles, cosedimentation, and electron microscopy analyses, provided evidence that C1 binding to E-LDL particles is mediated by the C1q globular domain, which senses unesterified fatty acids generated by cholesterol esterase. The potential implications of these findings in atherogenesis are discussed.

No MeSH data available.


Related in: MedlinePlus