C-Reactive Protein As a Mediator of Complement Activation and Inflammatory Signaling in Age-Related Macular Degeneration

Chirco, Kathleen R.; Potempa, Lawrence A.

doi:10.3389/fimmu.2018.00539

Cited by 32 publications

(27 citation statements)

References 64 publications

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“…Indeed, our data showed an upregulation of multiple APPs, including CRP and major attack complexes (MACs) in the severe sera. CRP can activate the complement system (Chirco and Potempa, 2018). This on the one hand leads to enhanced cytokine and chemokine production, potentially contributing to “cytokine storm”; and on the other overly recruits macrophages from the peripheral blood, which could result in acute lung injury(Chirco and Potempa, 2018; Narasaraju et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…CRP can activate the complement system (Chirco and Potempa, 2018). This on the one hand leads to enhanced cytokine and chemokine production, potentially contributing to “cytokine storm”; and on the other overly recruits macrophages from the peripheral blood, which could result in acute lung injury(Chirco and Potempa, 2018; Narasaraju et al, 2011). Because about 50% of platelets are produced in the lung (Lefrancais et al, 2017), platelet may in turn respond to lung injury and activate macrophases by degranulation (Mantovani and Garlanda, 2013), which may further add to “cytokine storm”.…”

Section: Discussionmentioning

confidence: 99%

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Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Shen

Sun

et al. 2020

Preprint

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24Severe COVID-19 patients account for most of the mortality of this disease. 25 Early detection and effective treatment of severe patients remain major 26 challenges. Here, we performed proteomic and metabolomic profiling of sera 27 from 46 COVID-19 and 53 control individuals. We then trained a machine 28 learning model using proteomic and metabolomic measurements from a 29 training cohort of 18 non-severe and 13 severe patients. The model correctly 30 classified severe patients with an accuracy of 93.5%, and was further 31 validated using ten independent patients, seven of which were correctly 32 classified. We identified molecular changes in the sera of COVID-19 patients 33 implicating dysregulation of macrophage, platelet degranulation and 34 complement system pathways, and massive metabolic suppression. This 35 study shows that it is possible to predict progression to severe COVID-19 36 disease using serum protein and metabolite biomarkers. Our data also 37 uncovered molecular pathophysiology of COVID-19 with potential for 38 developing anti-viral therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Shen

Sun

et al. 2020

Preprint

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“…Our data also revealed upregulation of multiple APPs, including CRP and major attack complexes (MACs) in the severe sera. CRP can activate the complement system (Chirco and Potempa, 2018). This, on the one hand, leads to enhanced cytokine and chemokine production, potentially contributing to ''cytokine storm''; and on the other hand, it overly recruits macrophages from the peripheral blood, which could result in acute lung injury (Chirco and Potempa, 2018;Narasaraju et al, 2011).…”

Section: Molecular Insights For the Pathogenesis Of Sars-cov-2 Infectionmentioning

confidence: 99%

“…CRP can activate the complement system (Chirco and Potempa, 2018). This, on the one hand, leads to enhanced cytokine and chemokine production, potentially contributing to ''cytokine storm''; and on the other hand, it overly recruits macrophages from the peripheral blood, which could result in acute lung injury (Chirco and Potempa, 2018;Narasaraju et al, 2011). Because about 50% of platelets are produced in the lung (Lefranç ais et al, 2017), platelets may in turn respond to lung injury and activate macrophages by degranulation (Mantovani and Garlanda, 2013), which may further add to cytokine storm.…”

Section: Molecular Insights For the Pathogenesis Of Sars-cov-2 Infectionmentioning

confidence: 99%

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Shen

Sun

et al. 2020

Cell

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Background: Recently, dyslipidaemia was observed in patients with coronavirus disease 2019 (COVID-19), especially in severe cases. This study aimed to explore the predictive value of blood lipid levels for COVID-19 severity. Methods: All patients with COVID-19 admitted to HwaMei Hospital, University of Chinese Academy of Sciences, from January 23 to April 20, 2020, were included in this retrospective study. General clinical characteristics and laboratory data (including blood lipid parameters) were obtained, and their predictive values for the severity were analysed. Results: In total, 142 consecutive patients with COVID-19 were included. The non-severe group included 125 cases, and 17 cases were included in the severe group. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (ApoA1) at baseline were signi cantly lower in the severe group. ApoA1 and interleukin-6 (IL-6) were recognized as independent risk factors for COVID-19 severity. ApoA1 had the highest area under the receiver operator characteristic curve (AUC) among all the single markers (AUC: 0.896, 95% CI: 0.834-0.941). Moreover, the risk model established using ApoA1 and IL-6 enhanced the predictive value (AUC: 0.977, 95% CI: 0.932-0.995). On the other hand, ApoA1 levels were elevated in the severe group during treatment, and there was no signi cant difference between the severe and non-severe groups during the recovery stage of the disease. Conclusion: The blood lipid pro le in severe COVID-19 patients is quite different from that in non-severe cases. Serum ApoA1 could severe as a good indictor to re ect the severity of COVID-19.

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“…Oxidative stress and elevated ROS levels have been claimed to increase the CRP level in various diseases [19,[28][29][30][31][32]. FH is involved in regulating the CS and known to correlate positively with CRP levels [33,34]. Moreover, CRP is able to inactivate the AP of the CS [35,36].…”

Section: Crp and Rage Coordinate Under Oxidative Stressmentioning

confidence: 99%

Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Gurubaran

Heloterä

Marry

et al. 2021

Biology

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Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

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C-Reactive Protein As a Mediator of Complement Activation and Inflammatory Signaling in Age-Related Macular Degeneration

Cited by 32 publications

References 64 publications

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

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