Disease relevance of CD55

• Mouse cells transfected with the CD55 clone bind echovirus 7, and this binding is blocked by the anti-receptor mAb [1].
• Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis [2].
• It has been shown that rituximab induces complement-mediated cytotoxicity in follicular lymphoma cells in vitro, and complement inhibitors CD55 and CD59 may regulate this process [3].
• Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia [4].
• Interestingly, in brains with chronic but not acute experimental autoimmune encephalomyelitis, C3b opsonization of neuronal cell bodies and axons was consistently associated with robust neuronal expression of one of the most effective complement regulators, decay-accelerating factor (CD55) [5].

Psychiatry related information on CD55

• Rates of cognitive impairment in a representative population of the oldest old (aged 84 to 90) were examined using two indicators: The Global Deterioration Scale (GDS), and a Cognitive Rating (CR) derived from performance on five neuropsychological tests [6].

High impact information on CD55

• Interaction with DAF also activates Fyn kinase, an event that is required for the phosphorylation of caveolin and transport of virus into the cell within caveolar vesicles [7].
• Here, we report that virus attachment to DAF on the apical cell surface activates Abl kinase, triggering Rac-dependent actin rearrangements that permit virus movement to the tight junction [7].
• The cell content of CD55 and CD59 was assessed by fluorescence-activated flow cytometry [8].
• Nevertheless, certain malignant cells, particularly those undergoing apoptotic stress, can activate homologous C, overcoming the regulatory actions of CD46 and/or CD55 [9].
• Decay-accelerating factor (DAF), a glycoprotein that is anchored to the cell membrane by phosphatidylinositol, binds activated complement fragments C3b and C4b, thereby inhibiting amplification of the complement cascade on host cell membranes [10].

Chemical compound and disease context of CD55

• CD55, a widely-distributed phosphatidyl inositol-anchored protein, was more frequently lost in NHL cells than in other types of hematological malignancies [11].
• The former group includes the sucrose hemolysis test for screening and Ham's acid hemolysis test for confirmation; the latter group includes FCM analyses of CD55 and CD59, which have recently replaced Ham's test, and FCM quantification of specific GPI-anchor binding using fluorescent-labeled inactive toxin aerolysin (FLAER) [12].
• We investigated whether exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia and/or reoxygenation activates complement and decreases HUVEC-surface expression of the C3 regulatory proteins CD46 and CD55 [13].
• Paroxysmal nocturnal hemoglobinuria is an acquired clonal expansion of bone marrow stem cells that are deficient in the decay-accelerating factor, which is a complement regulatory glycoprotein (CD55), as well as in the membrane inhibitor of reactive lysis (CD59) and the C8-binding protein [14].
• Prostaglandin E2 regulates the complement inhibitor CD55/decay-accelerating factor in colorectal cancer [15].

Biological context of CD55

• The human erythrocyte blood group system Cromer consists of high-incidence and low-incidence antigens that reside on decay-accelerating factor (DAF; CD55), a glycosyl-phosphatidylinositol-anchored membrane protein that regulates complement activation on cell surfaces [16].
• In contrast, the increase in cell death effected by neutralizing concentrations of anti-CD46 or anti-CD55 Ab was only 0.13- or 0.35-fold, respectively [17].
• We have used mutagenesis to map biological functions onto the molecule; decay-accelerating activity maps to a single face of the molecule, whereas bacterial and viral pathogens recognize a variety of different sites on CD55 [18].
• Afa/Dr diffusely adhering Escherichia coli infection in T84 cell monolayers induces increased neutrophil transepithelial migration, which in turn promotes cytokine-dependent upregulation of decay-accelerating factor (CD55), the receptor for Afa/Dr adhesins [19].
• Transfection of Chinese hamster ovary (CHO) cells with human CD55 resulted in a translocation of NF-kappa B after stimulation with LPS as well as with free lipid A [20].

Anatomical context of CD55

• Antiadhesive role of apical decay-accelerating factor (CD55) in human neutrophil transmigration across mucosal epithelia [21].
• Expression of decay-accelerating factor (CD55) of the complement system on human spermatozoa [22].
• Decay-accelerating factor (CD55) is expressed by neurons in response to chronic but not acute autoimmune central nervous system inflammation associated with complement activation [5].
• CD55 is overexpressed on some tumor cell lines, and in colorectal carcinomas, it has been shown to be an indicator of poor prognostic [23].
• High expression of CD55 was significantly associated with low-grade (grades 1 or 2; P = 0.001), lymph node negativity (P = 0.031), and good prognosis tumors (Nottingham Prognostic Index < 3.4; P < 0.001) [23].

Associations of CD55 with chemical compounds

• Decay-accelerating factor (DAF or CD55) is a 70-kDa glycosyl-phosphatidylinositol (GPI)-anchored protein that protects cells from complement-mediated lysis by either preventing the formation of or dissociating C3 convertases [24].
• Here, we demonstrate that CD55 is able to contribute to lipopolysaccharide (LPS) signaling [20].
• Human decay-accelerating factor (DAF, CD55) is a phosphatidyl inositol-anchored glycoprotein consisting, from the N-terminus, of 4 short consensus repeats (SCR), a Ser/Thr (ST)-rich region providing O-glycosylation sites, and the membrane-anchoring unit [25].
• Decay-accelerating factor (CD55) was present homogeneously on the basement membranes, on the basal cell border of the thyroid follicular cells, and often on the luminal surface of carcinoma cells [26].
• In conclusion, marathon running did not alter the expression of CD55 or CD59 on RBCs, despite concomitant elevations in blood bilirubin concentrations [27].

Physical interactions of CD55

• Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97 [28].
• EMR2 fails to interact with CD55, the cellular ligand for CD97, suggesting the possibility of a different cellular ligand(s) [29].
• The hearts from mice transgenic for human CD59 had substantially less and in some cases no membrane attack complex (MAC) and hearts from CD59/DAF transgenic mice had substantially less or no C5b and MAC [30].
• Selective inhibition of the two proteins on normal erythrocytes by the antisera demonstrated (i) that the factor responsible for accelerated decay of erythrocyte-bound C3 convertase is DAF and (ii) that the cofactor required for inactivation of erythrocyte-bound C3b by factor I is CR1 [31].
• Using an adenovirus transduction system, we demonstrate that CVA21 can remain infectious for up to 24 h after DAF binding and is capable of initiating a multicycle lytic infection upon delayed ICAM-1 surface expression [32].
• This suggests that CD55 might simultaneously regulate both the innate and adaptive immune responses, and we have shown that CD55 can still regulate complement when bound to CD97 [33].

Regulatory relationships of CD55

• The VEGF-induced DAF expression was functionally effective, significantly reducing complement-mediated EC lysis, and this cytoprotective effect was reversed by CsA [34].
• The findings suggest that adhesive activity of CD97 toward CD55 is unlikely to be regulated by differential CD97 isoform expression [35].
• Inhibition by flk-1 kinase inhibitor SU1498 and failure of placental growth factor (PlGF) to up-regulate DAF confirmed the role of VEGF-R2 [34].
• Production of transgenic pigs expressing human DAF (CD55) regulated by the porcine MCP gene promoter [36].
• Compared with controls, less MAC was deposited in many CD59-expressing hearts and less C5b and MAC in DAF-expressing hearts [30].

Other interactions of CD55

• Thus, CD46, CD55, and CD59 expression on pretreatment tumor cells, or their susceptibility to in vitro complement-mediated killing, does not predict clinical outcome after rituximab treatment [3].
• Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55) [37].
• This study investigated the effects of VEGF on CD55 deposition into matrix and the release of CD55 by metalloproteinases [38].
• RBC membrane molecules CD55 and CD59 along with phosphatydylserine and CD47 were measured [39].
• A functional analysis of recombinant soluble CD46 in vivo and a comparison with recombinant soluble forms of CD55 and CD35 in vitro [40].

Analytical, diagnostic and therapeutic context of CD55

• Furthermore, incorporation of membrane-bound complement regulators (decay-accelerating factor (CD55), membrane co-factor protein (CD46), CD59) in transgenic animals has provided a major step forward in protecting xenografts from hyperacute rejection [41].
• Molecular dissection of interactions between components of the alternative pathway of complement and decay accelerating factor (CD55) [42].
• The prognostic significance of CD55 was then investigated in these tumors using an anti-CD55 monoclonal antibody (RM1) that we raised against a synthetic peptide and a standard immunohistochemistry method [23].
• A recombinant soluble chimeric complement inhibitor composed of human CD46 and CD55 reduces acute cardiac tissue injury in models of pig-to-human heart transplantation [43].
• CONCLUSIONS: The CD55/CD59 transgenic porcine liver appears capable of safely "bridging" a patient to liver transplantation [44].

References