Complement activation on human neuroblastoma cell lines in vitro: route of activation and expression of functional complement regulatory proteins.
Two human neuroblastoma cell lines activated the classical pathway of complement in serum. Activation caused the opsonisation of these cells with complement fragments but with moderate cell killing. Neuroblastoma expressed regulators MCP and CD59 but did not express DAF or CR1. Neutralisation of CD59 rendered the cells susceptible to killing. Neuroblastoma also expressed C1-inhibitor, factor H, clusterin and S-protein. Expression of several regulators was enhanced by incubation with cytokines. Complement inhibition using soluble CRI markedly reduced opsonisation and killing of neuroblastoma. Our results suggest that complement might play a role in neuronal loss and that treatment with complement inhibitors might be of therapeutic value.
Gasque
P
P
Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, UK.
Thomas
A
A
Fontaine
M
M
Morgan
B P
BP
D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism*; D003167:Complement Activation; D003169:Complement Inactivator Proteins / Q000235:genetics / Q000378:metabolism; D003171:Complement Pathway, Classical; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000097:blood*; D015345:Oligonucleotide Probes / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011951:Receptors, Complement; D011994:Recombinant Proteins