20 KDa homologous restriction factor of complement resembles T cell activating protein

Okada, Hidechika; Nagami, Yoichi; Takahashi, Kazuhiro; Okada, Noriko; Hideshima, Teru; Takizawa, Hisao; Kondo, Jun

doi:10.1016/0006-291x(89)90852-8

Cited by 111 publications

(40 citation statements)

References 16 publications

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“…2). CD59, another GPI-anchored glycoprotein expressed on a wide range of cell types including monocytes (42,43), was not eliminated as efficiently as CD14 by gingipains, which excluded the possibility that gingipains preferentially cleave GPI-anchored molecules on the sell surface. When cells were incubated for longer period and with higher concentration (1 M KGP and HRGP for 30 min), the expression of TLR4 was unchanged, and CD18, CD59, and HLA-A, -B, -C expressions were reduced by about 10% compared with 0.3 M KGP and HRGP, whereas CD54 (ICAM-1) was relatively sensitive, but about 50% still remains on the cell surface after the treatment (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Proteolysis of Human Monocyte CD14 by Cysteine Proteinases (Gingipains) fromPorphyromonas gingivalisLeading to Lipopolysaccharide Hyporesponsiveness

Sugawara

Nemoto

Tada

et al. 2000

The Journal of Immunology

120

114

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Cysteine proteinases (gingipains) elaborated from Porphyromonas gingivalis exhibit enzymatic activities against a broad range of host proteins and are considered key virulence factors in the onset and development of adult periodontitis and host defense evasion. In this study, we examined the ability of arginine-specific gingipains (high molecular mass Arg-specific gingipain (HRGP) and Arg-specific gingipain 2) and lysine-specific gingipain (KGP) to cleave monocyte CD14, the main receptor for bacterial cell surface components such as LPS. Binding of anti-CD14 mAb MY4 to human monocytes was almost completely abolished by 0.3 M HRGP and KGP treatments for 15 min, and 1 M RGP2 for 30 min. In contrast, the expressions of Toll-like receptor 4, and CD18, CD54, CD59, and HLA-A, -B, -C on monocytes were slightly increased and decreased, respectively, by 0.3 M HRGP and KGP. This down-regulation resulted from direct proteolysis, because 1) gingipains eliminated MY4 binding even to fixed monocytes, and 2) CD14 fragments were detected in the extracellular medium by immunoblot analysis. Human rCD14 was degraded by all three gingipains, which confirmed that CD14 was a substrate for gingipains. TNF-␣ production by monocytes after HRGP and KGP treatments was decreased at 1 ng/ml, but not at 20 g/ml LPS, indicating that gingipains inhibited a CD14-dependent cell activation. These results suggest that gingipains preferentially cleave monocyte CD14, resulting in attenuation of the cellular recognition of bacteria, and as a consequence sustain chronic inflammation. The Journal of Immunology, 2000, 165: 411-418.A n oral chronic inflammation, i.e., periodontal disease, is one of the major diseases afflicting mankind and caused by a bacterial infection leading to gingival inflammation, destruction of periodontal tissues, loss of alveolar bone, and culminating in tooth loss (1, 2). Porphyromonas gingivalis has been implicated as a principal bacterium not only in adult periodontitis, but also in rapidly progressive periodontitis (1, 2). P. gingivalis possesses a number of putative virulence factors such as LPS, fimbriae, toxic products of metabolism, and proteinases, all of which enable this anaerobe to cause the disease either directly or indirectly by activation of host cells to release inflammatory mediators (3).It is now clear that all of the trypsin-like proteinase activity of P. gingivalis is due to two cysteine proteinases (4). Two types of cysteine proteinases specific for Arg-X (50 and 95 kDa) (5) and Lys-X (105 kDa) bonds have been purified and characterized and are referred to as arginine-specific gingipain (RGP) 3 (3) and lysine-specific gingipain (KGP), respectively (6). The 95-kDa high molecular mass RGP (HRGP or HRgpA) differs from the 50-kDa RGP (RGP2 or RgpB) in that the protein noncovalently complexes with the hemagglutinin/adhesin domain in the same manner as KGP. It has been shown that gingipains play a critical role in the onset of inflammation through enhancement of vascular permeability by activation of the kallikr...

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Section: Discussionmentioning

confidence: 99%

Proteolysis of Human Monocyte CD14 by Cysteine Proteinases (Gingipains) fromPorphyromonas gingivalisLeading to Lipopolysaccharide Hyporesponsiveness

Sugawara

Nemoto

Tada

et al. 2000

The Journal of Immunology

120

114

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“…The expression of complement regulatory proteins, such as membrane cofactor protein (CD46) (1), decay accelerating factor (CD55) (2), and CD59 (3,4) in transgenic pigs, has been shown to be very effective in protecting against hyperacute rejection in a xenograft (5)(6)(7)(8).…”

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confidence: 99%

Remodeling of the Major Pig Xenoantigen by N-Acetylglucosaminyltransferase III in Transgenic Pig

Miyagawa¹,

Murakami²,

Takahagi³

et al. 2001

Journal of Biological Chemistry

105

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We have been successful in generating several lines of transgenic mice and pigs that contain the human ␤-Dmannoside ␤-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene. The overexpression of the GnT-III gene in mice and pigs reduced their antigenicity to human natural antibodies, especially the Gal␣1-3Gal␤1-4Glc-NAc-R, as evidenced by immunohistochemical analysis. Endothelial cell studies from the GnT-III transgenic pigs also revealed a significant down-regulation in antigenicity, including Hanganutziu-Deicher antigen, and dramatic reductions in both the complement-and natural killer cell-mediated pig cell lyses. Changes in the enzymatic activities of other glycosyltransferases, such as ␣1,3-galactosyltransferase, GnT-IV, and GnT-V, did not support cross-talk between GnT-III and these enzymes in the transgenic animals. In addition, we demonstrated the effect of GnT-III in down-regulating the xenoantigen of pig heart grafts, using a pig to cynomolgus monkey transplantation model, suggesting that this approach may be useful in clinical xenotransplantation in the future.

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“…Complement-resistant retroviral vector (LRHL) was constructed by replacing the neomycin resistance gene (Neo R ) of the LRNL retroviral vector with the HRF20 13,14 (Figure 1). To produce virus-producing cells, LRHL retroviral vector was transduced into ⌿2 ecotropic packaging cells, and then the supernatant was poured into PA317 amphotropic packaging cells.…”

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confidence: 99%

Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene

et al. 1998

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Homologous restriction factor 20 (HRF20, CD59) is one of cessfully selected by complement-dependent selection, the complement regulatory factors. In this study, the which showed significant expression of the HRF20 antigen. complement-resistant retroviral vector, which possessesIn addition, these cells, transduced with tissue plasminthe HRF20 gene as a selection gene, was constructed and ogen activator (tPA) cDNA using complement-resistant examined. The virus-producing cell, transduced with retroviral vector, expressed tPA antigen after complementcomplement-resistant retroviral vector, was established dependent selection. These findings suggest that compafter complement-dependent selection. NIH3T3 and PK15 lement-resistant retroviral vector can be used for the cells transduced with this virus-producing cell were sucdouble transduction of HRF20, as well as other genes.Keywords: complement-dependent selection; gene therapy; retroviral vectorThe technique of gene transfer has been developed over the past decade and enables gene therapy to be applied to patients suffering from inherent metabolic diseases and malignancies. 1,2 The use of retroviral vectors is the most efficient method of gene therapy and their cDNA usually consists of both a therapeutic and a selection gene such as the neomycin-resistance gene or hygromycin-resistance gene. [3][4][5] Using these selection drugs, the retroviral vector-producing cells are selected 10 to 14 days after transduction. Recent investigation has demonstrated the effect of in vivo gene transfer with retroviral vector-producing cells on the treatment of experimental and clinical brain tumors using the herpes simplex virus thymidine kinase (HSVtk) gene, the mechanism of which has been termed the bystander effect. [6][7][8] However, it is difficult to introduce retroviral vector-producing cells in vivo for human gene therapy because of the immunological reaction to vector-producing cells by human complement. It has been reported that the homologous restriction factor 20 (HRF20, CD59) gene, one of the regulators of the complement activation (RCA) molecule, can be used for rapid selection of transduced cells. 9 Due to the transduction of the RCA molecule, xenogeneic cells are resistant to human complement attack. [10][11][12] To insert the HRF20 gene, as well as other therapeutic genes into vector-producing cells, the authors established a novel complement-resistant retroviral vector, which possesses the HRF20 gene as a selection gene.Complement-resistant retroviral vector (LRHL) was constructed by replacing the neomycin resistance gene (Neo R ) of the LRNL retroviral vector with the HRF20 (Figure 1). To produce virus-producing cells, LRHL retroviral vector was transduced into ⌿2 ecotropic packaging cells, and then the supernatant was poured into PA317 amphotropic packaging cells. After these cells were selected using complement-dependent selection, six colonies were grown. The expression of the HRF20 antigen on these cells was shown to be strongly positive, the mean channel shift ...

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20 KDa homologous restriction factor of complement resembles T cell activating protein

Cited by 111 publications

References 16 publications

Proteolysis of Human Monocyte CD14 by Cysteine Proteinases (Gingipains) fromPorphyromonas gingivalisLeading to Lipopolysaccharide Hyporesponsiveness

Proteolysis of Human Monocyte CD14 by Cysteine Proteinases (Gingipains) fromPorphyromonas gingivalisLeading to Lipopolysaccharide Hyporesponsiveness

Remodeling of the Major Pig Xenoantigen by N-Acetylglucosaminyltransferase III in Transgenic Pig

Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene

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