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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 Mol├ęculaire, 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

Electron micrographs of E-LDL-bound C1q molecules. (a, b) Examples of C1q molecules interacting through most of their globular domains (a) or only a few (b). (c) Representative example of a free C1q molecule (modified from [15], with permission).
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fig4: Electron micrographs of E-LDL-bound C1q molecules. (a, b) Examples of C1q molecules interacting through most of their globular domains (a) or only a few (b). (c) Representative example of a free C1q molecule (modified from [15], with permission).

Mentions: Negative staining electron microscopy was used to visualize interaction of the whole C1q molecule with E-LDL particles. Bound C1q molecules were clearly seen to interact with the particles through their globular domains. In some cases, most of the 6 globular domains were found to follow the curvature of the particles (Figure 4(a)), whereas other C1q molecules interacted through only a few heads (Figure 4(b)). Some free C1q molecules not interacting with E-LDL particles could also be identified (Figure 4(c)).


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

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

Electron micrographs of E-LDL-bound C1q molecules. (a, b) Examples of C1q molecules interacting through most of their globular domains (a) or only a few (b). (c) Representative example of a free C1q molecule (modified from [15], with permission).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Electron micrographs of E-LDL-bound C1q molecules. (a, b) Examples of C1q molecules interacting through most of their globular domains (a) or only a few (b). (c) Representative example of a free C1q molecule (modified from [15], with permission).
Mentions: Negative staining electron microscopy was used to visualize interaction of the whole C1q molecule with E-LDL particles. Bound C1q molecules were clearly seen to interact with the particles through their globular domains. In some cases, most of the 6 globular domains were found to follow the curvature of the particles (Figure 4(a)), whereas other C1q molecules interacted through only a few heads (Figure 4(b)). Some free C1q molecules not interacting with E-LDL particles could also be identified (Figure 4(c)).

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 Mol├ęculaire, 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