Inhibition of the Lytic Action of Cell-bound Terminal Complement Components by Human High Density Lipoproteins and Apoproteins

Rosenfeld, Stephen I.; Packman, Charles H.; Leddy, John P.

doi:10.1172/jci110833

Cited by 70 publications

(41 citation statements)

References 44 publications

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“…We found that the rHDL effect on TCC was specific to CC because no inhibition was observed on MSU crystals. Earlier in vitro studies showed that HDL, apoA-I, and apoA-II inhibited complementmediated lysis of erythrocytes (35). Recent analysis of the HDL proteome revealed that multiple complement components and complement regulatory proteins reside in HDL (36), raising the possibility of other protective roles of HDL on cells exposed to activated components of complement.…”

Section: Discussionmentioning

confidence: 99%

Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal–Induced Inflammatory Responses by Reducing Complement Activation

Niyonzima

Samstad

Aune

et al. 2015

The Journal of Immunology

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Chronic inflammation of the arterial wall is a key element in the development of atherosclerosis, and cholesterol crystals (CC) that accumulate in plaques are associated with initiation and progression of the disease. We recently revealed a link between the complement system and CC-induced inflammasome caspase-1 activation, showing that the complement system is a key trigger in CC-induced inflammation. HDL exhibits cardioprotective and anti-inflammatory properties thought to explain its inverse correlation to cardiovascular risk. In this study, we sought to determine the effect of reconstituted HDL (rHDL) on CC-induced inflammation in a human whole blood model. rHDL bound to CC and inhibited the CC-induced complement activation as measured by soluble terminal C5b-9 formation and C3c deposition on the CC surface. rHDL attenuated the amount of CC-induced complement receptor 3 (CD11b/CD18) expression on monocytes and granulocytes, as well as reactive oxygen species generation. Moreover, addition of CC to whole blood resulted in release of proinflammatory cytokines that were inhibited by rHDL. Our results support and extend the notion that CC are potent triggers of inflammation, and that rHDL may have a beneficial role in controlling the CC-induced inflammatory responses by inhibiting complement deposition on the crystals.

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Section: Discussionmentioning

confidence: 99%

Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal–Induced Inflammatory Responses by Reducing Complement Activation

Niyonzima

Samstad

Aune

et al. 2015

The Journal of Immunology

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“…As Y. enterocolitica binds inhibitors of the alternative and classical pathway (17,19,35), we first examined whether the bacteria could also use apoA-I in interference with the terminal complement pathway (11). Surprisingly, we found that apoA-I contributes to the bacterial killing in serum and that its complement inhibitory properties could not be used by the bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, studies with endothelial cells indicate that apoA-I may interfere with either insertion of C9 into a target membrane or with C9 polymerization at C5b-8 sites (11). Indeed, HDL has been shown to interfere with insertion of nascent fluid phase C5b-7 complexes to cell membranes (36).…”

Section: Discussionmentioning

confidence: 99%

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Apolipoprotein A-I Exerts Bactericidal Activity against Yersinia enterocolitica Serotype O:3

Biedzka-Sarek

Metso

Kateifides

et al. 2011

Journal of Biological Chemistry

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“…47 HDL has been reported to inhibit binding of the terminal complement complex to cell surfaces, interfering with either the insertion of C9 into the membrane or its polymerisation. 48 Halkes et al 49 have shown that C3 levels increase in humans after eating fat.…”

Section: Environmental Exposure and Complementmentioning

confidence: 99%

Complement in age-related macular degeneration: a focus on function

Bradley

Zipfel

Hughes

2011

Eye

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Age-related macular degeneration (AMD) is an inflammatory disease, which causes visual impairment and blindness in older people. The proteins of the complement system are central to the development of this disease. Local and systemic inflammation in AMD are mediated by the deregulated action of the alternative pathway of the complement system. Variants in complement system genes alter an individual's risk of developing AMD. Recent studies have shown how some risk-associated genetic variants alter the function of the complement system. In this review, we describe the evolution of the complement system and bring together recent research to form a picture of how changes in complement system genes and proteins affect the function of the complement cascade, and how this affects the development of AMD. We discuss the application of this knowledge to prevention and possible future treatments of AMD.

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Inhibition of the Lytic Action of Cell-bound Terminal Complement Components by Human High Density Lipoproteins and Apoproteins

Cited by 70 publications

References 44 publications

Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal–Induced Inflammatory Responses by Reducing Complement Activation

Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal–Induced Inflammatory Responses by Reducing Complement Activation

Apolipoprotein A-I Exerts Bactericidal Activity against Yersinia enterocolitica Serotype O:3

Complement in age-related macular degeneration: a focus on function

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