Immunohistochemical localization of the terminal C5b-9 complement complex in human aortic fibrous plaque

Vlaicu, R; Niculescu, Florin; Rus, Horea; Cristea, Anca

doi:10.1016/0021-9150(85)90030-9

Cited by 161 publications

(67 citation statements)

References 23 publications

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“…Complement activation to the level of C5b-9 has long been known to occur in atherosclerotic plaques (28,31), and several Igs, complement components, and regulators are present in atherosclerotic lesions, including IgG, IgM, C1q, and MBL (30,31). In C3- (26,49), C5-(50), C6- (29), and C1q-deficient (32) mice or rabbit models, reduced complement activity affected atherosclerotic development.…”

Section: Discussionmentioning

confidence: 99%

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Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin: Implications for the Progression of Atherosclerosis

Pilely

Rosbjerg

Genster

et al. 2016

The Journal of Immunology

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Cholesterol crystals (CC) play an essential role in the formation of atherosclerotic plaques. CC activate the classical and the alternative complement pathways, but the role of the lectin pathway is unknown. We hypothesized that the pattern recognition molecules (PRMs) from the lectin pathway bind CC and function as an upstream innate inflammatory signal in the pathophysiology of atherosclerosis. We investigated the binding of the PRMs mannose-binding lectin (MBL), ficolin-1, ficolin-2, and ficolin-3, the associated serine proteases, and complement activation products to CC in vitro using recombinant proteins, specific inhibitors, as well as deficient and normal sera. Additionally, we examined the deposition of ficolin-2 and MBL in human carotid plaques by immunohistochemistry and fluorescence microscopy. The results showed that the lectin pathway was activated on CC by binding of ficolin-2 and MBL in vitro, resulting in activation and deposition of complement activation products. MBL bound to CC in a calcium-dependent manner whereas ficolin-2 binding was calcium-independent. No binding was observed for ficolin-1 or ficolin-3. MBL and ficolin-2 were present in human carotid plaques, and binding of MBL to CC was confirmed in vivo by immunohistochemistry, showing localization of MBL around CC clefts. Moreover, we demonstrated that IgM, but not IgG, bound to CC in vitro and that C1q binding was facilitated by IgM. In conclusion, our study demonstrates that PRMs from the lectin pathway recognize CC and provides evidence for an important role for this pathway in the inflammatory response induced by CC in the pathophysiology of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

“…Complement activation and deposition of complement activation products occur both in experimental and human atherosclerosis (26)(27)(28)(29)(30)(31). Monohydrate CC, similar to those found in atherosclerotic plaques, activate the CP and the AP (3)(4)(5)7).…”

mentioning

confidence: 94%

Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin: Implications for the Progression of Atherosclerosis

Pilely

Rosbjerg

Genster

et al. 2016

The Journal of Immunology

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“…Deposition of complement components, C1q, C3, and C4, and generation of the terminal complement complex C5b-9 has been described in human atherosclerotic lesions [48]. The extent of C5b-9 deposition appears to correlate with the severity of the lesion [49], with the greatest deposition of iC3b reported in vulnerable and ruptured plaques [49,50]. Indeed, elevations in circulating C5a levels have been associated with increased cardiovascular risk in patients with advanced atherosclerosis [51].…”

Section: Discussionmentioning

confidence: 99%

Expression of complement components and inhibitors on platelet microparticles

2008

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Platelet microparticles (PMP) are released from activated platelets and play an important role in hemostasis, thrombosis and inflammation. Since platelets were recently found to demonstrate an intrinsic capacity for activating both classical and alternative pathways of the complement system, the present study extended these observations to PMP. PMP were generated by treating platelets with 10 µM A23187 (37°C, 5 min). PMP were identified by flow cytometry, based on size, Annexin V binding, and expression of P-selectin and GPIIb (CD41). PMP expressed gC1qR/p33, a multifunctional cellular protein that was recently described to activate the classical complement cascade. PMP also expressed the classical pathway and contact system regulator, CI inhibitor (C1-INH), as well as CD55 and CD59. Despite C1-INH expression, PMP supported classical pathway C4 activation in the presence of purified C1 and C4. Moreover, statistically significant deposition of C3b and C5b-9 was detected on PMP exposed to plasma, concurrently with expression of CD55 and CD59. These data provide the first evidence for the ability of PMP to support in situ complement activation. Complement activation contributes to a variety of vascular and inflammatory disease states including atherosclerosis and ischemia/reperfusion injury.

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“…The extent of C5b-9 deposition has been correlated with severity of the vascular lesion (Vlaicu, Niculescu, Rus and Cristea 1985). Moreover, iC3b deposition appears to be highest in vulnerable and ruptured plaques (Laine, Pentikainen, Wurzner, Penttila, Paavonen, Meri, and Kovanen 2002).…”

Section: Pathophysiology Of Platelet Mediated Complement Activationmentioning

confidence: 98%

Platelet Mediated Complement Activation

Peerschke

Ghebrehiwet

2008

Advances in Experimental Medicine and Biology

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Immunohistochemical localization of the terminal C5b-9 complement complex in human aortic fibrous plaque

Cited by 161 publications

References 23 publications

Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin: Implications for the Progression of Atherosclerosis

Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin: Implications for the Progression of Atherosclerosis

Expression of complement components and inhibitors on platelet microparticles

Platelet Mediated Complement Activation

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