Characterization <i>in vitro</i> and <i>in vivo</i> of the pig analogue of human CD59 using new monoclonal antibodies

Hanna, S. M.; Williams, Gareth T.; Berg, Carmen W. van den; Morgan, B. Paul

doi:10.1046/j.1365-2567.1998.00623.x

Cited by 14 publications

(24 citation statements)

References 19 publications

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“…mCD59a was expressed, albeit weakly, in the white matter of the brain and cerebellum, whereas in humans, rats and pigs, white matter was CD59‐negative 22–24 . Purkinje cells in the mouse cerebellum were negative for mCD59a, as reported in the pig 24 . Expression of mCD59a in kidney was similar to that in human, rat and pig; glomeruli, distal tubules and collecting ducts all expressed high levels of mCD59a 22–24 .…”

Section: Discussionmentioning

confidence: 64%

“…While, in most respects, the distribution of mCD59a was very similar to that of human CD59, there were interesting differences. mCD59a was expressed, albeit weakly, in the white matter of the brain and cerebellum, whereas in humans, rats and pigs, white matter was CD59‐negative 22–24 . Purkinje cells in the mouse cerebellum were negative for mCD59a, as reported in the pig 24 .…”

Section: Discussionmentioning

confidence: 79%

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Characterization of the mouse analogues of CD59 using novel monoclonal antibodies: tissue distribution and functional comparison

et al. 2003

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SUMMARYCD59, the sole membrane regulator of the membrane attack complex of complement, is broadly and abundantly expressed in man and other mammals. In mouse, CD59 is encoded by two homologous genes. The expression patterns and functional roles of the proteins encoded by these genes, mCD59a and mCD59b, have not been well characterized. Here we describe the generation of monoclonal and polyclonal antibodies detecting speci®cally mCD59a and mCD59b. These reagents have been used to study function and to ascertain the cell and tissue distributions of mCD59a and mCD59b. mCD59a was broadly distributed on endothelia, erythrocytes, platelets, and on numerous other cell types in organs, a distribution pattern resembling that of CD59 in other species. In marked contrast, expression of mCD59b was restricted to germ cell elements in the testis and mature spermatozoa. Both mCD59a and CD59b inhibited human and rodent complement with similar ef®ciency. These ®ndings demonstrate that the broadly distributed mCD59a is the key regulator of the terminal complement pathway in mice whereas CD59b, expressed only in testis and on sperm, probably plays other roles in vivo.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 79%

Characterization of the mouse analogues of CD59 using novel monoclonal antibodies: tissue distribution and functional comparison

et al. 2003

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“…8±10, 15 However, it has since been demonstrated that CD59 will inhibit C from many other species, sometimes more ef®ciently than it regulates homologous C. 11,12,31 Several studies have used blocking antibodies to address the capacity of human DAF to regulate activation of C on the cell surface.…”

Section: Discussionmentioning

confidence: 99%

Human and rodent decay‐accelerating factors (CD55) are not species restricted in their complement‐inhibiting activities

2000

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SUMMARYHomologous complement activation is restricted on cells by the complement regulators, decayaccelerating factor (DAF), membrane cofactor protein (MCP) and CD59. These proteins act in concert with other membrane structures to protect cells from homologous complement attack. In contrast, cells are usually sensitive to heterologous complement attack. It has been suggested that species-speci®c restriction of complement activation can be attributed to the inability of regulators to inhibit across species. We have investigated the capacities of human, rat and mouse analogues of DAF to regulate homologous and heterologous complement. Cells transfected with cDNA encoding these analogues were protected from heterologous complement attack. C3b-deposition experiments indicated that whilst cells were best protected by DAF from the same species, all three analogues inhibited human, rat and mouse complement. Comparable results were obtained in haemolysis assays using soluble, recombinant forms of the proteins. Inhibition of the classical pathway (CP) was best achieved with homologous DAF, although human DAF also inhibited rat complement, rat DAF also inhibited human complement and mouse DAF inhibited complement from all species. Human DAF was the best inhibitor of alternative pathway (AP)-mediated attack, inhibiting complement from all species. Mouse DAF inhibited mouse and rat AP, whilst rat DAF inhibited only rat AP. These data indicate that human and rodent analogues of DAF are not species restricted and highlights interesting differences in the capacity to regulate AP and CP. This has implications in broader ®elds of research, such as xenotransplantation, where cross-species regulation of complement is of paramount importance.

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“…Complement deposition on the grafts was determined by staining with rabbit anti-human C3b (Biogenesis) and mouse anti-human C5b-9 (DAKO). Staining for CD59 was performed using mouse anti-swine CD59 (MEL) that was generously provided by Dr. B. Paul Morgan of the University of Cardiff, UK (17). …”

Section: Methodsmentioning

confidence: 99%

Upregulation of CD59: Potential Mechanism of Accommodation in a Large Animal Model

Griesemer

Okumi²,

Shimizu³

et al. 2009

Transplantation

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Background Survival of ABO-mismatched kidneys with stable renal function despite the persistence of anti-ABO antibodies is called accommodation. The mechanism of accommodation is unclear, but may involve complement regulatory proteins such as CD59. The development of alpha-1,3-Galactosyltransferase knock-out (GalT-KO) swine that produce anti-Gal antibodies provides a large animal model capable of determining the role of complement regulatory proteins in accommodation. Methods ELISA and antibody FACS were used to examine the rate of anti-Gal antibody expression as a function of age. MHC-matched kidneys were transplanted from Gal-positive MGH miniature swine to MGH GalT-KO swine with systemic immunosuppression. One recipient underwent adsorbtion of anti-Gal antibodies prior to transplantation. Graft survival, antibody and complement deposition patterns and CD59 expression were determined. Results Three animals rejected Gal-positive kidneys via humoral mechanisms. One animal with low titers of anti-Gal Ab displayed spontaneous accommodation and the animal that was treated with Ab adsorbtion also displayed accommodation. Rejected grafts had deposition of IgM, IgG, C3 and C5b-9 with low expression of CD59, while accommodated grafts had low deposition of C5b-9 and high expression of CD59. Re-transplantation of one accommodated graft to a naïve GalT-KO animal confirmed that changes in the graft were responsible for the lack of C5b-9 deposition. Conclusion GalT-KO miniature swine produce anti-Gal antibodies and titers increase with age. These anti-Gal antibodies can cause rejection of MHC matched kidneys unless accommodation occurs. CD59 upregulation appears to be involved in the mechanism of accommodation by preventing the formation of the MAC on the accommodated graft.

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Characterization in vitro and in vivo of the pig analogue of human CD59 using new monoclonal antibodies

Cited by 14 publications

References 19 publications

Characterization of the mouse analogues of CD59 using novel monoclonal antibodies: tissue distribution and functional comparison

Characterization of the mouse analogues of CD59 using novel monoclonal antibodies: tissue distribution and functional comparison

Human and rodent decay‐accelerating factors (CD55) are not species restricted in their complement‐inhibiting activities

Upregulation of CD59: Potential Mechanism of Accommodation in a Large Animal Model

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