Complement Activation after Oxidative Stress

Collard, Charles D.; Väkevä, Antti; Morrissey, Margaret A.; Agah, Azin; Rollins, Scott A.; Reenstra, Wende R.; Buras, Jon A.; Meri, Seppo; Stahl, Gregory L.

doi:10.1016/s0002-9440(10)65026-2

Cited by 307 publications

(81 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from the above-mentioned experimental studies employing anti-MBL [67, 68] or anti-MASP-2 antibodies [65], the selective inhibition of the initial steps of the lectin pathway has not been fully investigated and lacks clinical evaluation. Rather, the attention has been turned to a potent complement inhibitor, C1-INH, widely used in the treatment of hereditary angioedema.…”

Section: Mbl In Cardiovascular Diseasementioning

confidence: 99%

Mannan-Binding Lectin in Cardiovascular Disease

Pągowska‐Klimek

Cedzyński

2014

BioMed Research International

View full text Add to dashboard Cite

Cardiovascular disease remains the leading cause of mortality and morbidity worldwide so research continues into underlying mechanisms. Since innate immunity and its potent component mannan-binding lectin have been proven to play an important role in the inflammatory response during infection and ischaemia-reperfusion injury, attention has been paid to its role in the development of cardiovascular complications as well. This review provides a general outline of the structure and genetic polymorphism of MBL and its role in inflammation/tissue injury with emphasis on associations with cardiovascular disease. MBL appears to be involved in the pathogenesis of atherosclerosis and, in consequence, coronary artery disease and also inflammation and tissue injury after myocardial infarction and heart transplantation. The relationship between MBL and disease is rather complex and depends on different genetic and environmental factors. That could be why the data obtained from animal and clinical studies are sometimes contradictory proving not for the first time that innate immunity is a “double-edge sword,” sometimes beneficial and, at other times disastrous for the host.

show abstract

Section: Mbl In Cardiovascular Diseasementioning

confidence: 99%

Mannan-Binding Lectin in Cardiovascular Disease

Pągowska‐Klimek

Cedzyński

2014

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…11 The immunologic damage to the cells lining the vasculature of organ allografts are thought to set a cascade of events in motion which ultimately lead to inappropriate antigen presentation to lymphocytes primed to attack the foreign organ. 12 The oxidative stress of ischemic injury on EC plays a major role in endothelial dysfunction and rapid development of vascular disease.…”

Section: Introductionmentioning

confidence: 99%

“…However, the oxidative insult experienced in transplantation is controllable since the time of reperfusion is controlled surgically, thus providing a larger window for therapeutic intervention. 11 Currently, no therapeutics are utilized to control IRI or the initiation of an adaptive immune response at this early time point post-transplantation.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

et al. 2015

View full text Add to dashboard Cite

In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses of endothelial cell (EC) inflammation when subjected to oxidative stress, such as observed in organ transplantation. Targeted Rapamycin Micelles (TRaM) were synthesized using PEG-PE-amine and N-palmitoyl homocysteine (PHC) with further tailoring of the micelle using targeting peptides (cRGD) and labeling with far-red fluorescent dye for tracking during cellular uptake studies. Our results revealed that the TRaM was approximately 10 nm in diameter and underwent successful internalization in Human Umbilical Vein EC (HUVEC) lines. Uptake efficiency of TRaM nanoparticles was improved with the addition of a targeting moiety. In addition, our TRaM therapy was able to downregulate both mouse cardiac endothelial cell (MCEC) and HUVEC production and release of the pro-inflammatory cytokines, IL-6 and IL-8 in normal oxygen tension and hypoxic conditions. We were also able to demonstrate a dose-dependent uptake of TRaM therapy into biologic tissues ex vivo. Taken together, these data demonstrate the feasibility of targeted drug delivery in transplantation, which has the potential for conferring local immunosuppressive effects without systemic consequences while also dampening endothelial cell injury responses.

show abstract

“…Lysis of parenchymal cells by the MAC (52), C3a- and C5a-induced recruitment of leukocytes through chemotaxis and production of inflammatory cytokines and chemokines (55) have been implicated as injury-mediating mechanisms in IRI. The critical role of the lectin activation pathway by mannose binding lectin (MBL) in renal IRI has been demonstrated in several experimental studies (56–58). Absence of MBL was shown to be protective against the adverse effects of renal IRI with significantly less tissue damage, while reconstitution of MBL aggravated injury.…”

Section: Innate Immune Responses Subsequent To Irimentioning

confidence: 99%

Ischemia/Reperfusion Injury and its Consequences on Immunity and Inflammation

et al. 2014

View full text Add to dashboard Cite

Ischemia/reperfusion injury (IRI), an inherent component of transplantation, affects organ quality and transplant outcomes. Although the complexity of the pathophysiology is recognized, detailed mechanisms remain unclear, and strategies preventing the consequences of IRI have been challenging. Of critical significance appears the link between IRI, the initiation of innate immune responses, and the (potential) augmentation of adaptive immunity. An improved understanding of those complex mechanisms and interactions may pave the way for more effective treatment strategies.

show abstract

Complement Activation after Oxidative Stress

Cited by 307 publications

References 31 publications

Mannan-Binding Lectin in Cardiovascular Disease

Mannan-Binding Lectin in Cardiovascular Disease

Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

Ischemia/Reperfusion Injury and its Consequences on Immunity and Inflammation

Contact Info

Product

Resources

About