Complement-dependent cellular cytotoxicity: lymphoblastoid lines that activate complement component 3 (C3) and express C3 receptors have increased sensitivity to lymphocyte-mediated lysis in the presence of fresh human serum.

Ramos, Olga; Sármay, Gabriella; Klein, Eva; Yefenof, Eitan; Gergely, J.

doi:10.1073/pnas.82.16.5470

Cited by 38 publications

(27 citation statements)

References 26 publications

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“…The implication of both Fc␥R and C1q in the in vivo antitumor effect of rituximab against CD20ϩ lymphoma cell lines has been clearly demonstrated in murine models (20,21), suggesting that ADCC and complement activation are essential for rituximab therapeutic effect. In addition, the fact that opsonization of target cells with complement components results in increased lysis by NK cells that express the CD11b/CD18 receptor (34,35) strongly suggests that ADCC and complement activation may have a cooperative activity in vivo (32,36). Complement-dependent cytotoxicity is mainly dependent on lymphoma cell variability, especially on both their CD20 and complement regulatory protein membrane expression (13,14,16), although response to rituximab therapy has been shown to be independent of the level of expression of these proteins on the tumor tissue (37).…”

Section: Discussionmentioning

confidence: 99%

Rituximab-Dependent Cytotoxicity by Natural Killer Cells

et al. 2004

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Finally, the functional difference between VV and FF NK cells was restricted to rituximab concentrations weakly sensitizing CD20. This study supports the conclusion that FCGR3A genotype is associated with response to rituximab because it affects the relationship between rituximab concentration and NK cell-mediated lysis of CD20؉ cells. Rituximab administration could therefore be adjusted according to FCGR3A genotype.

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Section: Discussionmentioning

confidence: 99%

Rituximab-Dependent Cytotoxicity by Natural Killer Cells

et al. 2004

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“…The molecules responsible for C3 deposition under these conditions remain unidentified. Another report has suggested that C3 deposition physiologically occurs in damaged cells for facilitating clearance by C receptor-positive leukocytes (43)(44)(45)(46). In fact, P39 + sublines were established through culture in conditions under which most cells died (18).…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of a human membrane protein that activates the alternative complement pathway and allows the deposition of homologous complement C3.

Matsumoto

Yamashita

Iida

et al. 1995

The Journal of Experimental Medicine

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SummaryA human myeloid cell subline, P39 +, is found to be a target for human complement (C) via the alternative pathway and to allow the deposition of multiple C3 fragments on its membranes, though expressing the complement regulatory proteins decay-accelerating factor and membrane cofactor protein. The parent cell line, P39-, which is phenotypically similar to the P39 + subline, does not allow the deposition of homologous C3 fragments. In this study, we established a monoclonal antibody, M161 Ab, which reacted with P39 + but not P39-cells. This Ab recognized a 43-kD protein in P39 + cell lysate transblotted onto nitrocellulose. Using this Ab as a probe, we purified the 43-kD protein, namely, M161 antigen (Ag). M161 Ag had a basic isoelectric point (pI), 9.3-9.4 by chromatofocusing, and was precipitated as an insoluble material at the pI point. The purified M161 Ag was a single-chain protein and did not possess N-or O-linked carbohydrates. When the purified M161 Ag was transblotted onto nitrocellulose and incubated with Mg2+-EGTA serum, human C3 fragments were efficiently deposited on M161 Ag. The major species of the deposited C3 fragments was C3b. Furthermore, the C3 fragments bound to the M161 Ag were detached by 1 M hydroxylamine, suggesting that a covalent ester linkage sustains M161 Ag-C3b interaction. NH2-terminal amino acid analysis revealed that M161Ag is a novel membrane protein. Hence, it appeared that M161 Ag is a potent activator of human alternative complement pathway on human cells that activates homologous C3 and allows the deposition of C3b on itself. Thus, under some conditions, homeostasis of complement is maintained even on human cells, not only by the complement regulatory proteins, but also by membrane C3-activating molecules on which C3b is deposited.

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“…The C3b and C3bi molecules on the cells enhance the phagocytic activity of complement receptor (CR1 and CR3)-bearing cells and facilitate the elimination of nonself cells by phagocytes (5,36). In addition to the destruction of cell surface M. fermentans, infected cells may be cleared from the host (27,41). However, all of the M. fermentans cells (PG18) were not killed by complement during 1 or 2 h of incubation in FS at 37°C (data not shown), suggesting that the organisms may escape complement attack by their rapid invasion of the cells and tissues and persistently infect host cells.…”

Section: Discussionmentioning

confidence: 99%

Complement Activation inMycoplasma fermentans-Induced Mycoplasma Clearance from Infected Cells: Probing of the Organism with Monoclonal Antibodies against M161Ag

et al. 2000

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Mycoplasma fermentans, a cell wall-less prokaryote, is capable of infecting humans and has been suggested to serve as a cofactor in AIDS development. Recently, we discovered a novel lipoprotein with a molecular mass of 43 kDa originating from M. fermentans. This protein, named M161Ag, activated human complement via the alternative pathway and efficiently induced the proinflammatory cytokines interleukin 1␤ (IL-1␤), tumor necrosis factor alpha, IL-6, IL-10, and IL-12 in human peripheral blood monocytes. It is likely that M161Ag of M. fermentans affects the host immune system upon mycoplasma infection. In this study, we developed monoclonal antibodies (MAbs) against M161Ag and examined the direct role of complement in M. fermentans infection using these MAbs as probes. M. fermentans was rapidly cleared from the surfaces of infected cells by human complement, but a low-grade infection persisted in human tumor cell lines. Mycoplasma particles remaining alive in host cells may cause recurrent infection, and liberated M161Ag may serve as a biological response modifier affecting both innate and acquired immunity.

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Complement-dependent cellular cytotoxicity: lymphoblastoid lines that activate complement component 3 (C3) and express C3 receptors have increased sensitivity to lymphocyte-mediated lysis in the presence of fresh human serum.

Cited by 38 publications

References 26 publications

Rituximab-Dependent Cytotoxicity by Natural Killer Cells

Rituximab-Dependent Cytotoxicity by Natural Killer Cells

Purification and characterization of a human membrane protein that activates the alternative complement pathway and allows the deposition of homologous complement C3.

Complement Activation inMycoplasma fermentans-Induced Mycoplasma Clearance from Infected Cells: Probing of the Organism with Monoclonal Antibodies against M161Ag

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