Activation of the alternative complement pathway by lymphoblastoid cell lines derived from patients with Burkitt's lymphoma and infectious mononucleosis

Budzko, Delia B.; Lachmann, P. J.; McConnell, Ian

doi:10.1016/0008-8749(76)90011-3

Cited by 101 publications

(41 citation statements)

References 7 publications

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“…The system can be activated by tumor cells through the alternative pathway [7] or the lectin pathway [8]. However, Ab-mediated activation of the classical pathway represents the most efficient way to target complement activation products to tumor cells in a sufficient quantity to cause cell damage.…”

Section: Introductionmentioning

confidence: 99%

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

et al. 2005

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Expression of the complement-regulatory proteins (CRP) CD46, CD55 and CD59 represents a strategy used by tumor cells to evade complement-dependent cell cytoxicity stimulated by monoclonal antibodies. We have isolated two single-chain variable fragments (scFv) to CD55 and CD59 from a human phage-display library and from these scFv we have produced two miniantibodies (MB), MB-55 (against CD55) and MB-59 (against CD59), containing the human hinge-CH2-CH3 domains of IgG1. The specificity of the two MB for the corresponding CRP was assessed by ELISA using purified CD46, CD55 and CD59. MB-55 and MB-59 neutralized the inhibitory activity of CD55 and CD59, respectively, restoring the complement-mediated lysis of sheep and guinea pig erythrocytes that was otherwise inhibited by the two CRP. FACS analysis revealed binding of MB-55 and MB-59 to the lymphoma cell line Karpas 422. The two MB induced a two-fold increase in the complement-dependent killing of these cells stimulated by Rituximab, a chimeric anti-CD20 monoclonal antibody. Transfection of HEK293T cells with vectors encoding MB-55 or MB-59 markedly reduced the expression of CD55 and CD59. We conclude that the human antibodies MB-55 and MB-59 may represent a therapeutic tool to increase the complement-dependent killing activity of Rituximab in the treatment of non-Hodgkin's lymphoma.

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Section: Introductionmentioning

confidence: 99%

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

et al. 2005

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“…However, we can not completely deny the participation of another pathway. Some types of tumor cells are well-known to activate the alternative pathway possibly releasing C3a and C5a (18,19). We could not determine how TPF-I participated in the dermal inflammation through the alternative pathway mechanism because Ca" chelators such as EGTA and EDTA, inhibitors of the classical pathway, showed irritability in the skin and disturbed evaluation of their inhibitory effects on TPF-I activity.…”

Section: Discussionmentioning

confidence: 96%

Characterization of Vascular Permeability-Increasing Component Isolated from Solid Tumors and the Effect of Highly Polymerized Dextran Sulfate on Its Activity

Sato

Niimura

Fujisawa

et al. 1986

Japanese Journal of Pharmacology

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Abstract-Increasein vascular permeability is usually seen at the growth site of a tumor implant in murine dermal tissue.Increased vascular permeability was inducible by the subcutaneous injection of a solid tumor extract rich in protein precipitable at 20-50% saturation of ammonium sulfate.The vascular permeability increasing activity of the tumor extract was reducible in the presence of highly polymerized dextran sulfate (DS-500) which showed a strong anti complementary activity, but not by other substances such as dextran sulfate with a low molecular weight, non-sulfated dextran, chondroitin sulfate or heparin.As the tumor extract includes r-globulins in aggregated or bound form and adsorbs complements, it is probable that the aggregated r-globulins increase vascular permeability by triggering the complement activation system in the skin. DS-500 might antagonize the process.

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“…It is well established that B lymphoblastoid cell lines infected with EBV can activate the AP. as shown with cell lines derived from patients with Burkitt's lymphoma [22][23][24]. In one study, deposition of C3 fragments, as a consequence of AP activation, has been demonstrated on mononuclear cells from patients with CLL, whereas cells from patients with other forms of leukaemia, or lymphocytes from normal individuals., were found not to do so [25].…”

Section: Introductionmentioning

confidence: 83%

Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL)

Marquart¹,

Grønbæk

Christensen

et al. 1995

Clinical and Experimental Immunology

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SUMMARYIt has previously been reported that the expression of Ihe complement receptors CR I (CD35) and CR2 (CD21) on malignant B cells in CLL is reduced compared with the expression on normal B cells, while deposition of eoniplenient C3 fragments, as a consequence ofalternative pathway (AP) activation of complement, is observed on mononuclear cells from patients with B CLL. Following our demonstration that normal B cells are capable of activating the AP of complement in a CR2-dependent fashion, we have chosen to re-examine the complement-activating ability of B CLL cells in relation to their altered phenotype with respect to CR2 and the complement regulatory membrane proteins. CRl. decay accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46). Flow cytometry was used to measure expression of complement receptors and regulatory proteins on CDS*" B cells from CLL patients, as well as the deposition of C3 fragments occurring both in vivo and after in vitro AP activation. We have confirmed the reduced expression of CRl and CR2 on CLL cells and have shown that AP activation in the presence of homologous, normal serum was reduced on B CLL cells compared with normal B cells. The degree of AP activation correlated directly with CR2 expression. In addition, we observed that CLL cells bear in v/ro-deposited C3d.g. although at a significantly lower level than normal B cells.

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Activation of the alternative complement pathway by lymphoblastoid cell lines derived from patients with Burkitt's lymphoma and infectious mononucleosis

Cited by 101 publications

References 7 publications

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

Characterization of Vascular Permeability-Increasing Component Isolated from Solid Tumors and the Effect of Highly Polymerized Dextran Sulfate on Its Activity

Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL)

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