Regulation of Complement and Contact System Activation via C1 Inhibitor Potentiation and Factor XIIa Activity Modulation by Sulfated Glycans – Structure-Activity Relationships

Schoenfeld, Ann-Kathrin; Lahrsen, Eric; Alban, Susanne

doi:10.1371/journal.pone.0165493

Cited by 27 publications

(24 citation statements)

References 61 publications

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“…Indeed, the treatment of B16 melanoma cells, Sarcoma-180 and Lewis lung carcinoma cells with oversulfonated fucoidans from F. vesiculosus revealed better anti-proliferative effect than the treatment with native fucoidans, thus emphasizing the importance of this structural feature for the antitumor activity of these polysaccharides [15]. Imunomodulatory [113] anticomplementary [114] or anti-angiogenetic [115] activity are examples of other bioactivities described for fucoidans for which molecular weight and sulfonation degree have been shown to be determinant. …”

Section: Nutrient Composition Of Fucus Sppmentioning

confidence: 99%

Phycochemical Constituents and Biological Activities of Fucus spp.

2018

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Seaweeds are known to be a good supply of key nutrients including carbohydrates, protein, minerals, polyunsaturated lipids, as well as several other health-promoting compounds capable of acting on a wide spectrum of disorders and/or diseases. While these marine macroalgae are deeply rooted in the East Asian culture and dietary habits, their major application in Western countries has been in the phycocolloid industry. This scenario has however been gradually changing, since seaweed consumption is becoming more common worldwide. Among the numerous edible seaweeds, members of the genus Fucus have a high nutritional value and are considered good sources of dietary fibers and minerals, especially iodine. Additionally, their wealth of bioactive compounds such as fucoidan, phlorotannins, fucoxanthin and others make them strong candidates for multiple therapeutic applications (e.g., antioxidant, anti-inflammatory, anti-tumor, anti-obesity, anti-coagulant, anti-diabetes and others). This review presents an overview of the nutritional and phytochemical composition of Fucus spp., and their claimed biological activities, as well as the beneficial effects associated to their consumption. Furthermore, the use of Fucus seaweeds and/or their components as functional ingredients for formulation of novel and enhanced foods is also discussed.

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Section: Nutrient Composition Of Fucus Sppmentioning

confidence: 99%

Phycochemical Constituents and Biological Activities of Fucus spp.

2018

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“…Interactions between C1INH and heparin have been reported to augment rhC1INH activity 5‐ to 11‐fold and potentiate the inhibitory effect on C1‐dependent activation of the complement cascade . The synergistic effect between rhC1INH and heparin has been previously shown to enhance inhibition of the CP, LP, and AP in human samples in a dose‐dependent fashion . We exploited this interaction to maximize complement inhibition in donors in our model.…”

Section: Discussionmentioning

confidence: 99%

“…G3 donors received only continuous IV heparin infusion as described with dosing titrated to a partial thromboplastin time of 80‐120 seconds. Heparin was used to potentiate the activity of rhC1INH as described previously …”

Section: Methodsmentioning

confidence: 99%

Targeted donor complement blockade after brain death prevents delayed graft function in a nonhuman primate model of kidney transplantation

Danobeitia¹,

Zens²,

Chlebeck³

et al. 2020

American Journal of Transplantation

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Delayed graft function (DGF) in renal transplant is associated with reduced graft survival and increased immunogenicity. The complement-driven inflammatory response after brain death (BD) and posttransplant reperfusion injury play significant roles in the pathogenesis of DGF. In a nonhuman primate model, we tested complement-blockade in BD donors to prevent DGF and improve graft survival.BD donors were maintained for 20 hours; kidneys were procured and stored at 4°C for 43-48 hours prior to implantation into ABO-compatible, nonsensitized, MHC-mismatched recipients. Animals were divided into 3 donor-treatment groups: G1 -vehicle, G2 -rhC1INH+heparin, and G3 -heparin. G2 donors showed significant reduction in classical complement pathway activation and decreased levels of tumor necrosis factor α and monocyte chemoattractant protein 1. DGF was diagnosed in 4/6 (67%) G1 recipients, 3/3 (100%) G3 recipients, and 0/6 (0%) G2 recipients (P = .008). In addition, G2 recipients showed superior renal function, reduced sC5b-9, and reduced urinary neutrophil gelatinase-associated lipocalin in the first week posttransplant. We observed no differences in incidence or severity of graft rejection between groups. Collectively, the data indicate that donor-management targeting complement activation prevents the development of DGF. Our results suggest a pivotal role for complement activation in BD-induced renal injury and postulate complement blockade as a promising strategy for the prevention of DGF after transplantation. 1514 | DANOBEITIA ET Al. K E Y W O R D S animal models: nonhuman primate, complement biology, delayed graft function (DGF), donors and donation: donation after brain death (DBD), immunosuppression/immune modulation, ischemia reperfusion injury (IRI), kidney transplantation/nephrology, translational research/ science 1 | INTRODUC TI ON Delayed graft function (DGF) manifests as a consequence of ischemia-reperfusion injury (IRI) and is characterized by acute kidney injury (AKI) within 7 days of transplant, requiring life-sustaining dialysis. 1 The incidence of DGF in kidney transplants from brain dead (BD) donors is approximately 26% in the United States, and this rate can reach as high as 37% in kidneys from older donors and those subjected to extended cold ischemia >36 hours. 2-4 In addition to complications related to AKI in the peritransplant period, development of DGF is an important risk factor for acute cellular rejection, antibody-mediated rejection (AMR), and reduced

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“…The KKS is also coupled to the complement system by the C1 Inhibitor (C1INH). The C1INH is a serine protease that inhibits the KKS via the inactivation of factor XIIa and kallikrein and inhibits the complement system via the inactivation of C1r and C1s of the classical pathway [ 18 - 20 ]. Interaction of KKS, RAAS and complement system in the development of angioedema has been illustrated in Figure 1 .…”

Section: Reviewmentioning

confidence: 99%

“…Normally, C1INH inhibits the complement system and the KKS. The C1INH suppression will increase spontaneous activation of the classical pathway of the complement and anaphylatoxins production (C3a, C4a, C5a) [ 18 ]. Anaphylatoxins will cause vascular permeability and vasodilation [ 16 ].…”

Section: Reviewmentioning

confidence: 99%

Pathogenesis of Drug Induced Non-Allergic Angioedema: A Review of Unusual Etiologies

Kalambay¹,

Ghazanfar²,

Pena³

et al. 2017

Cureus

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Angioedema is the swelling of mucosal and sub-mucosal tissue. Typically, it manifests as the swelling of the face, lips, and tongue. Angioedema can be severe and life threatening when it involves the respiratory tract. Drug induced allergic angioedema and drug induced non-allergic angioedema differ in their mediator, their clinical presentations, and their management. In drug induced non-allergic angioedema, symptoms are resistant to antihistamine and corticosteroid treatment. The aim of the analysis was to identify which medications are associated with drug-induced non-allergic angioedema and to understand the mechanism of action via which of these medication cause angioedema.

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Regulation of Complement and Contact System Activation via C1 Inhibitor Potentiation and Factor XIIa Activity Modulation by Sulfated Glycans – Structure-Activity Relationships

Cited by 27 publications

References 61 publications

Phycochemical Constituents and Biological Activities of Fucus spp.

Phycochemical Constituents and Biological Activities of Fucus spp.

Targeted donor complement blockade after brain death prevents delayed graft function in a nonhuman primate model of kidney transplantation

Pathogenesis of Drug Induced Non-Allergic Angioedema: A Review of Unusual Etiologies

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