Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complement (C) regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), which control C3 convertases, together with CD59, an inhibitor of the membrane attack complex (MAC), were found to be present in the developing human placenta from at least 6 weeks of gestation until term. Immunostaining revealed differences in the distribution of these proteins on the fetally derived trophoblast epithelium, especially in early placentae which contain trophoblast populations of diverse proliferative potential and differentiation status. Expression of all three proteins occurred on the terminally differentiated syncytiotrophoblast epithelium covering chorionic villi and which is in direct contact with maternal blood. CD59 was also expressed on the underlying villous cytotrophoblast cells and on their extra-villous derivatives. These two populations showed differential expression of the C3 convertase regulators. Villous cytotrophoblast cells expressed MCP but were largely devoid of DAF. Proliferation of this population to generate extra-villous cytotrophoblast cell columns was associated with both an increase in DAF expression and a decrease in MCP expression. Throughout placental development, expression of DAF appeared to be lower than that of MCP and CD59 as assessed by solid-phase binding assays on isolated trophoblast membranes. Early placentae were also found to contain both DAF+ and DAF- chorionic villi. Conversely, expression of CD59 appeared comparatively high and transcripts for CD59 were found to be much more abundant than those for DAF in purified trophoblast cells. C regulatory proteins appear to play an important role throughout gestation in protecting the fetally derived human conceptus from maternal C. The differential expression patterns of the proteins on trophoblast may reflect differences in requirement for specific functional activities at different locations within the placenta.
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PMID:Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of CD59 by comparison with membrane cofactor protein (CD46) and decay accelerating factor (CD55). 137 64

Levels of the membrane complement regulatory proteins, C3b/C4b receptor (CR1, CD35), membrane cofactor protein (MCP, CD46), and decay-accelerating factor (DAF, CD55), expressed on cells from patients with haematological malignancies and normal subjects were assessed by flowcytometry using the respective monoclonal antibodies (mAbs). All myeloid and most lymphoid leukaemia samples tested were CR1-negative: two of the 42 leukaemia samples expressed minute amounts of CR1. Lack of CR1 in leukaemia cells was confirmed with two mAbs raised against CR1, 31R, and 243R, which recognized different epitopes and induced different degrees of CR1-mediated fluorescent shift on flow-cytometry in granulocytes and erythrocytes. MCP was increased in most chronic myelogenous leukaemia (CML) and chronic lymphocytic leukaemia (CLL), and was also increased in majority of acute nonlymphocytic leukaemia (ANLL), acute lymphocytic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). Levels of DAF were also high in CML and CLL, and were variable in other types of leukaemia: some were DAF-negative while others expressed extremely high levels of DAF. In CML patients, the high level of MCP and the lack of CR1 were normalized after medical treatment. These results are in agreement with the data obtained with human leukaemia cell lines, and support the hypothesis that CR1 is essentially a differentiated cell antigen and that a high level of MCP reflects some malignant transformation or an immature stage in blood cells.
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PMID:Levels of complement regulatory proteins, CD35 (CR1), CD46 (MCP) and CD55 (DAF) in human haematological malignancies. 138 49

Most human nucleated cells and cell lines possess C3 step regulators, decay-accelerating factor (DAF; CD55) and membrane cofactor protein (MCP; CD46) and an inhibitor of membrane attack complex (MAC) formation (p18; CD59). Unless DAF and MCP were simultaneously blocked by their antibodies, Mg(2+)-EGTA-human serum treatment did not induce C3 deposition on most nucleated cells. Furthermore, less than 20% lysis occurred even after the block of all the three factors. In contrast, three myeloid cell lines, U-937, HL-60 and p39, were found to exhibit unusual C3 deposition or cytolysis. U-937 possessed DAF and MCP but lacked p18, and about 50% was lysed by treatment with anti-DAF and anti-MCP followed by Mg(2+)-EGTA-serum, which caused C3, C5 and C8 deposition. Anti-DAF evoked similar but less complement (C) deposition and cytolysis while anti-MCP alone did not, although it enhanced the anti-DAF-mediated C deposition and cytolysis. Thus, once the C3 step is overcome, U-937 is attacked by the late components leading to cytolysis because of the absence of p18. On the other hand, HL60 allowed the deposition of C3 by blocking of either DAF or MCP followed by the Mg(2+)-EGTA-serum treatment. C5, C8 and C9 were subsequently deposited but resulted in no lysis. Lysis of 60% was attained by the additional blocking of p18. Thus, HL60 is poorly protected by C3 and C9 step regulation. Strikingly, extensive C3 deposition occurs on p39 without any antibody treatment, suggestive of the presence of unique alternative pathway activators. However, little cytolysis was induced on p39 even by blocking of all three inhibitors with antibodies. These results suggest that in activation of the alternative pathway on myeloid cells, C3 step is controlled by the inhibitors and alternative pathway activators, and C-mediated cytolysis is blocked by p18 and additional regulatory mechanisms or factors which assist in protection of nucleated host cells from MAC attack. Susceptibility to homologous C of these cell lines, therefore, reflects relatively low potency of C regulation on their membrane.
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PMID:Alternative complement pathway-mediated myeloid cell cytotoxicity: repertoire of membrane factors participating in regulation of C3 deposition and cytolysis. 171 91

A natural killer (NK) target, K562 (a human erythroblastoid cell line), was found by flow cytometry to express three complement regulatory membrane proteins on its surface: decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and p18 (CD59). We examined the effects of F(ab')2 of polyclonal antibodies raised against DAF and MCP and monoclonal antibody to p18 on the susceptibility of K562 to cytolysis by homologous lymphocytes, granulocytes and complement. C3bi-deposition was induced on K562 when the cells were treated with both anti-DAF and anti-MCP. Lymphocyte-mediated K562 cytolysis was markedly enhanced by these two antibodies whereas anti-p18 barely affected the degree of cytolysis. Complement immunocytolysis, on the other hand, became highest by combination treatment with the three antibodies, although anti-p18 and either anti-DAF or anti-MCP induced little potentiation of cytolysis. Granulocytes showed the least cytolysis and minimal potentiation of lysis by treatment with both anti-DAF and anti-MCP.
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PMID:Enhancement of lymphocyte-mediated K562 cytotoxicity by antibodies against complement membrane cofactor protein (CD46) and decay-accelerating factor (CD55). 171 46

C3-deposition is a key step for activation of the complement system, which involves C9-mediated immunocytolysis, immunoadherence, C3 receptor-mediated phagocytosis, NK potentiation, anaphylatoxin release, and amplification of C3 activation. Foreign material is eliminated even in the preimmune stage by these complement functions. Self cells, on the other hand, must circumvent the C3-attack, so that they express complement regulatory proteins, namely C3b/C4b receptor (CR1, CD35), decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46). We herein review the properties of these regulatory proteins and discuss the relationships between disease processes and the aberrance of these regulatory proteins.
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PMID:[Cell-associated complement regulatory proteins and their relation to disease processes]. 172 33

The structural genes of human complement regulatory proteins are clustered on chromosome 1 at position q3.2. Human chromosome 1 was transferred into a mouse fibroblast cell line, A9 [designated as A9(neo-1)], and the surface expression of its gene products participating in complement regulation, namely C3b/C4b receptor (CR1, CD35), decay-accelerating factor (DAF, CD55), membrane co-factor protein (MCP, CD46) and C3d/EB virus receptor (CR2, CD21), were assessed using respective monoclonal antibodies by flow cytometry. CR1 became positive within 7 days of culture. MCP appeared in a small population of cells by Day 3 and, together with DAF, began to increase on Day 7. CR2 appeared on Day 14. The order of the expression was CR1 greater than DAF = MCP greater than CR2. On Day 42, however, all became negative except for MCP, which was markedly diminished. These human regulatory proteins were specifically associated with the presence of human chromosome 1, since none of them were expressed on human chromosome 12-transferred A9 cells [A9(neo-12)]. Intact A9 and A9(neo-12) cells activated human complement via the alternative pathway. The activation of this pathway was suppressed in the A9(neo-1) cells that expressed CR1, DAF and MCP. Slight protective activity was still observed in the 42-day cultured A9(neo-1) cells expressing only trace MCP. These results suggest that human complement regulators, expressed via the transferred human chromosome 1, can protect heterologous cells from complement, overcoming their ability to activate the human alternative pathway.
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PMID:Human complement regulatory proteins expressed on mouse A9 cells containing a human chromosome 1. 172 16

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. A mAb, named D17, was raised against purified erythrocyte-DAF. This mAb recognized DAF on blood cells and most cell lines as determined by flow cytometry and immunoblotting. Its reactivity was similar to but weaker than that of two other well-characterized mAbs to DAF, IA10 (seeing an epitope within SCR1) and 1C6 (seeing an epitope within SCR3). The reactivity of D17 with erythrocyte DAF became increased by treatment with sialidase/O-glycanase, suggesting that its epitope is located close to the O-glycosylation sites, probably within the ST-rich region or SCR4. D17 barely blocked the decay-accelerating activity of DAF. Using the three mAbs, tissue-associated and soluble forms of DAF were identified by SDS-PAGE/immunoblotting and immunohistochemical staining. IA10 and 1C6 recognized a 50 kDa protein in spermatozoa lysate and two proteins of Mr 70 and 55 kDa, respectively, in seminal fluid. These represented membrane-associated and soluble forms of DAF, which were neither recognized by mAb against membrane cofactor protein (MCP, CD46) and C3b/C4b receptor (CR1, CD35) nor by non-immune IgG. In contrast to IA10 and 1C6, D17 did not recognize either spermatozoa-DAF or seminal plasma-DAF, or the deglycosylated or untreated forms of them. Immunohistochemical analysis showed that testis was stained with IA10 but not with D17.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A monoclonal antibody against human decay-accelerating factor (DAF, CD55), D17, which lacks reactivity with semen-DAF. 750 2

Decay-accelerating factor (DAF) is a membrane protein that protects host cells from attack by its own complement. Although DAF expression on endothelial cells is thought to increase pathophysiologically, little is known about the natural mediators that modulate DAF expression on endothelial cells. In this study, we evaluated the effect of histamine on DAF expression on human umbilical vein cells (HUVEC). HUVEC were cultured with histamine, and DAF expression on HUVEC was determined by flow cytometry after immunostaining with a mAb to DAF. DAF expression on HUVEC was increased at 10 microM histamine, and the final level was increased time-dependently by 150% to 200% after a 24-h incubation with 100 microM histamine. The histamine-induced DAF expression was inhibited by actinomycin D and cycloheximide and accompanied by an increase in the DAF mRNA level, indicating that both transcription and translation are required. In addition, the histamine-induced DAF expression was inhibited by pyrilamine, an H1 blocker, but not by cimetidine, an H2 blocker, indicating that histamine induces the DAF expression through H1 receptors. We also demonstrated that the turnover of DAF is faster than that of MCP and CD59, and DAF is released into the culture supernatant. DAF is a glycosylphosphatidylinositol-linked protein that is released from HUVEC by a phosphatidylinositol-specific phospholipase C. Although HUVEC also contain the glycosylphosphatidylinositol-anchored complement inhibitor CD59, this was not released during a 24-h incubation, suggesting that the shedding of DAF from HUVEC is not caused by PI-PLC but by other enzymes, possibly proteinases. These results suggest that histamine, which is released from mast cells and basophils by complement-derived anaphylatoxins, increases the complement defense ability of endothelial cells by increasing their levels of DAF expression.
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PMID:Decay-accelerating factor on human umbilical vein endothelial cells. Its histamine-induced expression and spontaneous rapid shedding from the cell surface. 750 66

U937 cells are known to be relatively sensitive to C-mediated killing and have been reported to show variable expression of CD59. We have obtained stable CD59+ and CD59- sublines of the U937 cell line. Expression of other C-regulatory proteins, decay-accelerating factor (DAF), MCP and CR1, was similar on both cell lines. Although the sublines were morphologically similar and expressed similar amounts of most surface antigens, qualitative difference in expression of CD13 and CD64 and a quantitative difference in CD15 expression was observed. Sensitivity to C-mediated killing of the cell lines was measured using classical pathway activation. Both cell lines appeared to be equally sensitive to C-mediated killing. Monoclonal antibodies against CD59, which neutralize CD59 and enhance killing of most cell lines (including K562, HL60 and Molt4), did not enhance the killing of the CD59- cells but, surprisingly, also did not enhance killing of the CD59+ U937 subline. CD59 was expressed on the U937 subline at similar levels to that on HL60 and K562 cells, was glycosylphosphatidylinositol (GPI) anchored and could be immunoprecipitated from cell extracts. However, unlike these other cell lines, U937 cell extracts were negative in a Western blot using a variety of anti-CD59 antibodies even when ultrasensitive detection methods were used. These results indicate that the CD59+ U937 cell expresses a form of CD59 which is dysfunctional and structurally abnormal.
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PMID:Presence of a dysfunctional form of CD59 on a CD59+ subclone of the U937 cell line. 751 99

Experimental data have established that HIV-infected lymphocytes activate the complement system. However, because mammalian lymphocytes possess a series of cell-surface complement regulators that inhibit amplification on autologous cells, complement-mediated destruction of host cells is usually inhibited. These studies were performed to examine whether alterations in the cell-surface complement regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46) may occur during HIV infection in vitro or in vivo. The physiologic significance of these alterations were assessed by radiolabeled chromium release experiments. We show that MCP fluorescent intensity is significantly lessened in HIV-infected children and that DAF intensity is similarly lessened in infected children with advanced disease. These findings could be duplicated with HIV infection of peripheral blood mononuclear cells in vitro.
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PMID:Diminished expression of cell-surface complement regulatory proteins in HIV-infected children and with HIV infection of peripheral blood mononuclear cells in vitro. 754 Apr 89


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