A C3(H20) recycling pathway is a component of the intracellular complement system

Elvington, Michelle; Liszewski, M. Kathryn; Bertram, Paula; Kulkarni, Hrishikesh S.; Atkinson, John P.

doi:10.1172/jci89412

Cited by 97 publications

(109 citation statements)

References 40 publications

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“…Since these early − and so far limited − studies indicate that the amounts of intracellular C3 (activation) can hold the key to modulating T cell effector activity, it is now important to understand how C3 gene expression and protein generation is regulated. Interestingly, it was recently demonstrated that at least part of the intracellular C3 is transported from the extracellular milieu (serum/blood) into T and B cells (Elvington et al, 2017). This observation was in agreement with earlier report demonstrating that C3 can be internalized in Ca 2+ dependent manner via the lipoprotein-receptor-related protein/α2-macroglobulin receptor in mouse fibroblasts (Meilinger et al, 1999).…”

Section: Intracellular Complement Activation: the 'C3 And C5 Complosome'supporting

confidence: 91%

Intracellular complement − the complosome − in immune cell regulation

Arbore

Kemper

Kolev

2017

Molecular Immunology

175

158

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The complement system was defined over a century ago based on its ability to "complement" the antibody-mediated and cell-mediated immune responses against pathogens. Today our understanding of this ancient part of innate immunity has changed substantially and we know now that complement plays an undisputed pivotal role in the regulation of both innate and adaptive immunity. The complement system consists of over 50 blood-circulating, cell-surface expressed and intracellular proteins. It is key in the recognition and elimination of invading pathogens, also in the removal of self-derived danger such as apoptotic cells, and it supports innate immune responses and the initiation of the general inflammatory reactions. The long prevailing classic view of complement was that of a serum-operative danger sensor and first line of defence system, however, recent experimental and clinical evidences have demonstrated that "local" tissue and surprisingly intracellular complement (the complosome) activation impacts on normal cell physiology. This review will focus on novel aspects of intracellular complement activation and its unexpected roles in basic cell processes such as metabolism. We also discuss what the existence of the complosome potentially means for how the host handles intracellular pathogens such as viruses.

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Section: Intracellular Complement Activation: the 'C3 And C5 Complosome'supporting

confidence: 91%

Intracellular complement − the complosome − in immune cell regulation

Arbore

Kemper

Kolev

2017

Molecular Immunology

175

158

View full text Add to dashboard Cite

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“…An intracellular complement system has been observed also in fibroblasts, endothelial and epithelial cells, although the mechanisms underlying its activation and regulation and its functional outcomes are largely unexplored 17 . A rapid and saturable recycling pathway has been identified for C3 in lymphocytes that allows for exchange between intracellular stores and extracellular sources 18 .…”

Section: Complement Regulation Of the Host Responsementioning

confidence: 99%

“…The identity of the opsonizing C3 split products and the uptake receptor(s) involved in these mechanisms have not been specified. Since different cell types contain intracellular C3 that may be cleaved into C3a and C3b 13,18 , the above-discussed cell autonomous immune mechanisms could potentially be triggered even by intracellular pathogens that have escaped extracellular C3b opsonization.…”

Section: Complement In Homeostatic Immunity and Microbial Evasionmentioning

confidence: 99%

Novel mechanisms and functions of complement

et al. 2017

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Progress in the beginning of the 21st century transformed our perception of complement from a blood-based antimicrobial system to a global regulator of immunity and tissue homeostasis. More recent years have witnessed remarkable advances regarding structure-function insights, mechanisms and locations of complement activation, thereby adding new layers of complexity in the biology of complement. This complexity is readily reflected by the multifaceted and contextual involvement of complement-driven networks in a wide range of inflammatory and neurodegenerative disorders and cancer. This Review provides an updated view of new and previously unanticipated functions of complement and how these impact immunity and disease pathogenesis.

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“…This uptake alters activated CD4 + T‐cell cytokine secretion. Under stable conditions, most (80%) of the incorporated C3 is returned to the extracellular space …”

Section: Intracellular Complementmentioning

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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A C3(H20) recycling pathway is a component of the intracellular complement system

Cited by 97 publications

References 40 publications

Intracellular complement − the complosome − in immune cell regulation

Intracellular complement − the complosome − in immune cell regulation

Novel mechanisms and functions of complement

The complex functioning of the complement system in xenotransplantation

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