Beyond the Role of CD55 as a Complement Component

Dho, So Hee; Lim, Jae Cheong; Kim, Lark Kyun

doi:10.4110/in.2018.18.e11

Cited by 79 publications

(73 citation statements)

References 87 publications

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“…CD55 inhibits the formation of the C3-convertase, the major amplification step in the complement activation cascade and plays a critical role in negating complement-mediated injury in the pathophysiology of various inflammatory diseases including allograft rejection [24][25][26][27][28][29][30][31][32][33]. Here, we proposed to investigate a possible relationship between the key activated complement factor C3, and CD55, which is normally expressed on vascular endothelium and is the focus of the ongoing research plan.…”

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confidence: 99%

Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants

et al. 2020

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Background: Complement Regulatory Proteins (CRPs), especially CD55 primarily negate complement factor 3-mediated injuries and maintain tissue homeostasis during complement cascade activation. Complement activation and regulation during alloimmune inflammation contribute to allograft injury and therefore we proposed to investigate a crucial pathological link between vascular expression of CD55, active-C3, T cell immunity and associated microvascular tissue injuries during allograft rejection. Methods: Balb/c→C57BL/6 allografts were examined for microvascular deposition of CD55, C3d, T cells, and associated tissue microvascular impairments during rejection in mouse orthotopic tracheal transplantation. Results: Our findings demonstrated that hypoxia-induced early activation of HIF-1α favors a cell-mediated inflammation (CD4 + , CD8 + , and associated proinflammatory cytokines, IL-2 and TNF-α), which proportionally triggers the downregulation of CRP-CD55, and thereby augments the uncontrolled release of active-C3, and Caspase-3 deposition on CD31 + graft vascular endothelial cells. These molecular changes are pathologically associated with microvascular deterioration (low tissue O 2 and Blood flow) and subsequent airway epithelial injuries of rejecting allografts as compared to non-rejecting syngrafts. Conclusion: Together, these findings establish a pathological correlation between complement dysregulation, T cell immunity, and microvascular associated injuries during alloimmune inflammation in transplantation.

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confidence: 99%

Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants

et al. 2020

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“…Overexpression of the membrane-associated C regulatory proteins (mCRPs) CD46, CD55, and CD59 is another mechanism by which cancer cells can evade undesired C attack due to spontaneous or Ab-induced C activation. The mCRPs act at different steps of the C sequence by favoring the decay of the C3 convertases (CD55), promoting the degradation of C3b and C4b (CD46), and preventing the assembly of MAC (CD59) ( 66 , 67 ). Because of their high expression level on several tumors, mCRPs are considered promising targets for cancer immunotherapy.…”

Section: Complement-mediated Cancer Cell Damage and Regulationmentioning

confidence: 99%

“…CD46 has been shown to be highly expressed on colorectal, breast ( 68 ), prostate, lung, liver, and ovarian carcinoma ( 69 ) cancer cells. Elevated levels of CD55 have been documented in a wide range of cancers including lung, colorectal, gastric, breast, and cervical cancers as well as in leukemia ( 66 ). CD59 is also overexpressed on different types of carcinoma and sarcoma and on melanoma cells ( 70 ).…”

Section: Complement-mediated Cancer Cell Damage and Regulationmentioning

confidence: 99%

Complement as a Biological Tool to Control Tumor Growth

2018

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Deposits of complement components have been documented in several human tumors suggesting a potential involvement of the complement system in tumor immune surveillance. In vitro and in vivo studies have revealed a double role played by this system in tumor progression. Complement activation in the cancer microenvironment has been shown to promote cancer growth through the release of the chemotactic peptide C5a recruiting myeloid suppressor cells. There is also evidence that tumor progression can be controlled by complement activated on the surface of cancer cells through one of the three pathways of complement activation. The aim of this review is to discuss the protective role of complement in cancer with special focus on the beneficial effect of complement-fixing antibodies that are efficient activators of the classical pathway and contribute to inhibit tumor expansion as a result of MAC-mediated cancer cell killing and complement-mediated inflammatory process. Cancer cells are heterogeneous in their susceptibility to complement-induced killing that generally depends on stable and relatively high expression of the antigen and the ability of therapeutic antibodies to activate complement. A new generation of monoclonal antibodies are being developed with structural modification leading to hexamer formation and enhanced complement activation. An important progress in cancer immunotherapy has been made with the generation of bispecific antibodies targeting tumor antigens and able to neutralize complement regulators overexpressed on cancer cells. A great effort is being devoted to implementing combined therapy of traditional approaches based on surgery, chemotherapy and radiotherapy and complement-fixing therapeutic antibodies. An effective control of tumor growth by complement is likely to be obtained on residual cancer cells following conventional therapy to reduce the tumor mass, prevent recurrences and avoid disabilities.

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“…A deficiency of C55 and C59 can affect erythrocyte haemolysis and additionally stimulate the coagulation process, which is evident in patients with paroxysmal nocturnal haemoglobinuria . The abnormal expression of the CD55 molecule, alone or together with complement regulator proteins, is observed in various disease states: haemoglobinopathies, autoimmune haemolytic anaemia, anaemia accompanying malaria infection and HIV infection .…”

Section: Introductionmentioning

confidence: 99%

Selected CD molecules and the phagocytosis of microvesicles released from erythrocytesex vivo

et al. 2019

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Background and objectives The accumulation of microvesicles in erythrocyte concentrates during storage or irradiation may be responsible for clinical symptoms such as inflammation, coagulation and immunization. Our aim was to determine whether any of the cluster of differentiation (CD) molecules responsible for important functions are present on microvesicles, and if their expression level is dependent on the storage period of erythrocyte concentrates. Material and methods Erythrocyte microvesicles were isolated from ‘fresh’ (2nd day) and ‘old’ (42nd day) stored erythrocyte concentrates. Qualitative cytometric analysis of 0·5 µm, erythrocyte‐derived, PS‐exposing vesicles was performed using the annexin V‐FITC, anti‐CD235a‐PE antibody and calibrated beads. The microvesicles were also visualized under a confocal microscope. The expression of the molecules CD235a, CD44, CD47, CD55, CD59 and of phosphatidylserine (PS) was compared using flow cytometry. Measurements of microvesicle phagocytosis by human monocytes were carried out using a flow cytometer and a confocal microscope. Results The analysis of the microvesicles with calibration beads allowed us to identify these structures with a diameter of about 0·5 µm in the ‘fresh’ and ‘old’ samples. At day 2, the microvesicles had elevated expression levels of CD47, reduced expression levels of PS, CD55 and CD59. The phagocytosis index was higher for the microvesicles isolated from the 42‐day‐old erythrocyte concentrates. Conclusion This research may bring us closer to understanding the factors responsible for erythrocyte ageing and to evaluate the quality of stored red blood concentrates intended for transfusion.

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Beyond the Role of CD55 as a Complement Component

Cited by 79 publications

References 87 publications

Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants

Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants

Complement as a Biological Tool to Control Tumor Growth

Selected CD molecules and the phagocytosis of microvesicles released from erythrocytesex vivo

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