CD59 expressed by human endothelial cells functions as a protective molecule against complement‐mediated lysis

Ra, Brooimans; Aa, Van der Ark; Tomita, Motowo; La, van Es; Mr, Daha

doi:10.1002/eji.1830220324

Cited by 59 publications

(41 citation statements)

References 30 publications

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“…The PI fraction, released by the deamination procedure, was recovered by two extractions with 200 l and one extraction with 100 l of butan-1-ol saturated with water. The combined butan-1-ol phases were washed with 300 l of water, dried under a stream of N 2 and redissolved in 100 l of chloroform/methanol (2:3) containing 1 mM NH 3 . Aliquots (20 l) were introduced into the electrospray source of a Micromass (Altringham, Cheshire, UK) mass spectrometer in a stream of the same solvent at 10 l/min.…”

Section: Methodsmentioning

confidence: 99%

The Glycosylation of the Complement Regulatory Protein, Human Erythrocyte CD59

Rudd

Morgan

Wormald

et al. 1997

Journal of Biological Chemistry

164

103

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Section: Methodsmentioning

confidence: 99%

The Glycosylation of the Complement Regulatory Protein, Human Erythrocyte CD59

Rudd

Morgan

Wormald

et al. 1997

Journal of Biological Chemistry

164

103

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“…CD59 restricts homologous lysis by binding to the C8 and C9 molecules during the MAC formation, thus disturbing the C8: C9 ratio in the MAC complex (Meri et al, 1990;Lachmann, 1991). CD59 is broadly expressed in human tissues, in human blood cells and neoplastic haematopoietic cell lines (Davies et al, 1989), vascular endothelia (Brooismans et al, 1992), various ductal epithelia, in kidney, lung, skin and placenta (Lachmann, 1991;Meri et al, 1991;Rooney et al, 1991), in thyroid follicular cells (Tandon et al, 1992), and spermatozoa (Rooney et al, 1992). However, CD59 might be involved in other immune regulatory mechanisms, such as signal transduction in cells (Stefanova et al, 1991) and T-cell activation and adhesion (Deckert et al, 1992;Venneker & Asghar, 1992) where it functions as a second ligand for CD2 (Hahn et al, 1992).…”

mentioning

confidence: 99%

Expression of CD59, a complement regulator protein and a second ligand of the CD2 molecule, and CD46 in normal and neoplastic colorectal epithelium

Koretz

Brüderlein²,

Henne³

et al. 1993

Br J Cancer

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SummaryCD59 (protectin) and CD46 (membrane cofactor protein, MCP) are membrane-bound complement regulator proteins which inhibit complement-mediated cytolysis of autologous cells. CD59, a phosphatidyl-inositol-anchored glycoprotein, inhibits the formation of the terminal membrane attack complex (MAC) of complement and was found to be a second ligand for CD2 contributing to T-cell activation. In 20 colorectal normal mucosa samples, in ten adenomas, 71 carcinomas and in ten liver metastases derived thereof, CD59 was inconsistently expressed in the epithelial compartment. In carcinomas CD59 expression in the whole neoplastic compartment was more often found in well-and moderately differentiated tumours. By contrast, focal expression or even complete lack of CD59 was more often found in poorly differentiated tumours (P = 0.021). In addition, carcinomas without metastases at the time of operation (Dukes A/B) more often expressed CD59 in the entire neoplastic population compared to those carcinomas which had already metastasised (P = 0.018). There was no correlation between the mode of CD59 expression in colorectal carcinomas and the tumour type or location. CD46 has C3b/C4b binding and factor-I dependent cofactor activity and is broadly expressed in various cells and tissues. In the epithelial compartment of normal colorectal mucosa, of all adenomas, carcinomas and their liver metastases, CD46 was expressed throughout the epithelial compartment.Since CD46 was consistently expressed in colorectal carcinomas the low expression or even lack of CD59 in a subset of tumours might not lead to critical complement-mediated attack of CD59-negative tumour cells. Regarding CD59 as a natural T-cell ligand involved in cognate T-cell -target-cell interaction, however, loss of CD59 might well be a selection advantage, provided that tumour antigen-mediated T-cell toxicity in colorectal carcinoma exists.Membrane-bound regulatory proteins protect autologous cells from complement mediated cytotoxicity when fragments of the complement cascade are deposited on host cells which are not the desired target (Davitz, 1986). These proteins regulate the coordinating points in the classic and alternative pathways, the formation of the C3 convertases and the assembly of the terminal membrane attack complex (MAC) (Kinoshita, 1991). One of these proteins which aids in regulating the latter is protectin or CD59 (Hadam, 1989a), an 18-20 kD phosphatidyl-inositol anchored glycoprotein (Meri et al., 1990;Ratnoff et al., 1992). CD59 restricts homologous lysis by binding to the C8 and C9 molecules during the MAC formation, thus disturbing the C8: C9 ratio in the MAC complex (Meri et al., 1990;Lachmann, 1991 Asghar, 1992) where it functions as a second ligand for CD2 (Hahn et al., 1992). One protein which helps regulate the formation of the C3 convertases on autologous cells (Kinoshita, 1991) and the C5 convertase of the alternative complement pathway (Seya et al., 1991) is the 45-70 kD membrane cofactor protein (MCP) (Lublin & Atkinson, 1989) or CD46 (H...

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“…For example, we see phosphorylation of Cbl upon CD59 activation, yet activation of CD14 (the GPIlinked lipopolysaccharide receptor) by bacterial lipopolysaccharide does not result in Cbl phosphorylation. 3 In addition, PP1 inhibits phosphorylation from CD59 activation but has no effect on CD14 signaling, despite their colocalization in detergent-insoluble microdomains.…”

Section: Cd59-mediated Signal Transductionmentioning

confidence: 98%

“…It is abundantly expressed on a wide variety of cells, including many cells of hematopoietic lineage (2)(3)(4)(5), and functions to inhibit complement-mediated lysis by interfering with the assembly of the membrane attack complex and the insertion of complement 9 into the cell membrane (reviewed in Ref. 6).…”

mentioning

confidence: 99%

Antibody Cross-linking of the Glycosylphosphatidylinositol-linked Protein CD59 on Hematopoietic Cells Induces Signaling Pathways Resembling Activation by Complement

Murray

Robbins

1998

Journal of Biological Chemistry

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CD59 is a glycosylphosphatidylinositol-anchored cell surface glycoprotein involved in protecting cells from host-mediated complement attack. Studies have shown that antibody cross-linking of CD59 induces a series of intracellular signaling events including the activation of protein-tyrosine kinases (PTK). To further characterize these events, antibodies and complement 8, one of the natural ligands of CD59, were used to activate CD59. Antibody-induced cross-linking of CD59 on the surface of THP-1 and U937 hematopoietic cell lines as well as exposure to complement 8 induces a rapid increase in the tyrosine phosphorylation of several proteins within the cell. Consistent with an early role for the Src family PTKs in these signaling events, we found that transient activation of Hck-and CD59-mediated signaling was abrogated in the presence of the Src family PTK-selective inhibitor PP1. Although the molecular mechanism by which CD59 communicates to Hck is unknown, cellular fractionation studies indicated that both CD59 and Hck are compartmentalized in plasma membrane microdomains. We also detected tyrosine phosphorylation of the adaptor proteins p120 cbl and Shc, and the cytoplasmic nonreceptor tyrosine kinase Syk. The identification of CD59-mediated signaling events may help explain why paroxysmal nocturnal hemoglobinuria patients, who are deficient in glycosylphosphatidylinositol-linked proteins including CD59, are susceptible to proliferative disorders.CD59 is one of a large family of proteins that are attached to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol (GPI) 1 moiety attached to their C-terminal ends (1). It is abundantly expressed on a wide variety of cells, including many cells of hematopoietic lineage (2-5), and functions to inhibit complement-mediated lysis by interfering with the assembly of the membrane attack complex and the insertion of complement 9 into the cell membrane (reviewed in Ref.6). The natural ligands for CD59 include the ␣-chain of complement 8 (C8) and the "b" domain of complement 9 (7).Antibody-mediated cross-linking of CD59 on various hematopoietic cells induces a cascade of intracellular signaling activities including events such as calcium influx and release of calcium from intracellular stores, generation of reactive oxygen intermediates (8 -12), and induction of tyrosine phosphorylation (13,14). These events are not unique to CD59, since many other GPI-anchored proteins induce a series of similar intracellular signaling events when cross-linked or upon binding of appropriate ligand. Other GPI-linked molecules expressed on hematopoietic cells include the lipopolysaccharide receptor (CD14) (15, 16) and THY-1, a regulatory molecule in T-cell activation (17, 18).Since GPI-anchored proteins adhere to cells through their acyl chains and do not span the membrane, the mechanism by which this family of proteins transduce their signal into the cell remains unknown. However, GPI-linked proteins have been shown to cluster in detergent-insoluble glycolipid-enriche...

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CD59 expressed by human endothelial cells functions as a protective molecule against complement‐mediated lysis

Cited by 59 publications

References 30 publications

The Glycosylation of the Complement Regulatory Protein, Human Erythrocyte CD59

The Glycosylation of the Complement Regulatory Protein, Human Erythrocyte CD59

Expression of CD59, a complement regulator protein and a second ligand of the CD2 molecule, and CD46 in normal and neoplastic colorectal epithelium

Antibody Cross-linking of the Glycosylphosphatidylinositol-linked Protein CD59 on Hematopoietic Cells Induces Signaling Pathways Resembling Activation by Complement

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