The role and regulation of complement activation as part of the thromboinflammation elicited in cell therapies

Nilsson, Bo; Teramura, Yuji; Ekdahl, Kristina Nilsson

doi:10.1016/j.molimm.2014.06.009

Cited by 23 publications

(21 citation statements)

References 52 publications

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“…The cells are then exposed to thiolated apyrase (apyrase‐SH), which is immobilized on the cell surface via the maleimide‐PEG‐phospholipid. It is also possible to immobilize the recombinant soluble domain of CD39 (NTPDase‐1, EC 3.6.1.5), which continuously degrades vascular ADP on EC …”

Section: Examples Of Thromboinflammation In Therapeutic Medicinementioning

confidence: 99%

“…It is also possible to immobilize the recombinant soluble domain of CD39 (NTPDase-1, EC 3.6.1.5), which continuously degrades vascular ADP on EC. 2,203 For the regulation of the complement system, regulatory peptides are immobilized onto the cell surface in the same way. We have used functional peptides, which interact with complement regulators in blood such as factor H and C4BP.…”

Section: Modification Of Biosurfaces With Bioactive Molecules To Inmentioning

confidence: 99%

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Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross‐talk act as a linchpin in the events leading to thromboinflammation

Ekdahl

Teramura

Hamad

et al. 2016

Immunological Reviews

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130

127

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Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.

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Section: Examples Of Thromboinflammation In Therapeutic Medicinementioning

confidence: 99%

Section: Modification Of Biosurfaces With Bioactive Molecules To Inmentioning

confidence: 99%

Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross‐talk act as a linchpin in the events leading to thromboinflammation

Ekdahl

Teramura

Hamad

et al. 2016

Immunological Reviews

Self Cite

130

127

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“…Since thrombosis and inflammation occur in numerous vessels and organs under several pathological conditions, including vascular inflammation [8, 35], ischemia/reperfusion injury [36, 37], transfusion-related acute lung injury [38], atherosclerosis [39, 40], and cell transplantation and therapies [41], understanding of the detailed mechanisms mediating thromboinflammation could lead to the identification of an effective therapeutic target. In this review, we will focus on major surface receptors and signaling pathways that regulate heterotypic platelet–neutrophil interactions under thromboinflammatory conditions and also summarize how the platelet–neutrophil interaction participates in the initiation and propagation of the disease.…”

Section: Introductionmentioning

confidence: 99%

Platelet–neutrophil interactions under thromboinflammatory conditions

Kim

Barazia

et al. 2015

Cell. Mol. Life Sci.

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Platelets primarily mediate hemostasis and thrombosis, whereas leukocytes are responsible for immune responses. Since platelets interact with leukocytes at the site of vascular injury, thrombosis and vascular inflammation are closely intertwined and occur consecutively. Recent studies using real-time imaging technology demonstrated that platelet–neutrophil interactions on the activated endothelium are an important determinant of microvascular occlusion during thromboinflammatory disease in which inflammation is coupled to thrombosis. Although the major receptors and counter receptors have been identified, it remains poorly understood how heterotypic platelet–neutrophil interactions are regulated under disease conditions. This review discusses our current understanding of the regulatory mechanisms of platelet– neutrophil interactions in thromboinflammatory disease.

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“…The complement and coagulation systems share some trigger molecules. For example, C1q and Factor XII recognize negatively charged molecules (DNA, lipopolysaccharides, and heparin) . These two systems also share some regulators, for example, C1‐INH, an inhibitor of the CP and LP, also acts as a modulator of the coagulation contact system (factor XIa, factor XIIa, and kallikrein),and the fibrinolytic system (tissue plasminogen activator and plasmin) .…”

Section: Interaction Of Complement With Coagulation Factors and Platementioning

confidence: 99%

The complex functioning of the complement system in xenotransplantation

Zhou

Hara

Cooper

2019

Xenotransplantation

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The role of complement in xenotransplantation is well-known, and is a topic that has been reviewed previously. However, our understanding of the immense complexity of its interaction with other constituents of the innate immune response and of the coagulation, adaptive immune, and inflammatory responses to a xenograft is steadily increasing. In addition, the complement system plays a function in metabolism and homeostasis. New reviews at intervals are therefore clearly warranted. The pathways of complement activation, the function of the complement system, and the interaction between complement and coagulation, inflammation, and the adaptive immune system in relation to xenotransplantation are reviewed. Through several different mechanisms, complement activation is a major factor in contributing to xenograft failure. In the organ-source pig, the detrimental influence of the complement system is seen during organ harvest and preservation, e.g., in ischemia-reperfusion injury. In the recipient, the effect of complement can be seen through its interaction with the immune, coagulation, and inflammatory responses. Genetic-engineering and other therapeutic methods by which the xenograft can be protected from the effects of complement activation are discussed. The review provides an updated source of reference to this increasingly complex subject.

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The role and regulation of complement activation as part of the thromboinflammation elicited in cell therapies

Cited by 23 publications

References 52 publications

Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross‐talk act as a linchpin in the events leading to thromboinflammation

Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross‐talk act as a linchpin in the events leading to thromboinflammation

Platelet–neutrophil interactions under thromboinflammatory conditions

The complex functioning of the complement system in xenotransplantation

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