Abstract
The ion permeability of planar lipid bilayers, as measured electrically, was found to increase modestly upon treatment with purified complement complex C5b,6 and complement components C7 and C8. The subsequent addition C9 greatly amplified this change. No permeability changes occurred when components were added individually to the membrane, or when they were used in paired combinations, or when C5b, C7, C8, and C9 were admixed prior to addition. Thus, there is a significant parallel between the permeability changes induced in the model membrane and damage produced in biological membranes by the C5b-9 complement attack sequence. The efficiency of membrane action by C5b-9 was critically dependent on the order in whcih components were added to the membrane. There were also differences in the electrical properties of membranes treated with C5b-8 and C5b-9, though in both cases the enhanced bilayer permeability is best attributed to the formation of trans-membrane channels. Collectively, the data are consistent with the hypothesis that the mechanism of membrane action by complement involves the production of a stable channel across the lipid bilayer, resulting in cell death by colloid-osmotic lysis.
MeSH Terms
Cell Membrane Permeability/drug effects
Complement C5/pharmacology
Complement C6/pharmacology
Complement C7/pharmacology
Complement C8/pharmacology
Complement C9/pharmacology
Complement System Proteins/pharmacology
Electric Conductivity
Ions
Kinetics
Membranes, Artificial
Chemicals
Complement C5
Complement C6
Complement C7
Complement C8
Complement C9
Ions
Membranes, Artificial
Complement System Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Michaels D W
Abramovitz A S
Hammer C H
Mayer M M
References (25)
25 references, click to expand
-
Binding of the complement intermediate C56 to zymosan in acute phase human sera.
Clin Exp Immunol. 1975 Apr;20(1):113-24
PMID: 1106918
-
The nature of the voltage-dependent conductance induced by alamethicin in black lipid membranes.
J Membr Biol. 1973 Dec 31;14(2):143-76
PMID: 4774545
-
Mechanism of cytolysis by complement.
Proc Natl Acad Sci U S A. 1972 Oct;69(10):2954-8
PMID: 4117012
-
The ninth component of guinea-pig complement. Isolation and identification as an alpha 2-globulin.
Immunology. 1971 Mar;20(3):415-25
PMID: 4101489
-
Immune lytic transformation: a state of irreversible damage generated as a result of the reaction of the eighth component in the guinea pig complement system.
J Immunol. 1968 Jan;100(1):46-54
PMID: 4169697
-
Reactive lysis: the complement-mediated lysis of unsensitized cells. II. The characterization of activated reactor as C56 and the participation of C8 and C9.
J Exp Med. 1970 Apr 1;131(4):643-57
PMID: 4193935
-
Step conductance increases in bilayer membranes induced by antibody-antigen-complement action.
Biochim Biophys Acta. 1975 Dec 1;413(2):317-21
PMID: 1238122
-
Studies concerning the possible reconstitution of an active cation pump across an artificial membrane.
J Membr Biol. 1972;8(4):363-88
PMID: 4263932
-
Molecular analysis of the reaction of C9 with EAC1-8: reaction of C9 with EAC1-8.
J Immunol. 1974 Dec;113(6):1992-2003
PMID: 4214868
-
Reaction mechanisms of nascent C567 (reactive lysis). II. Killing of a rough form of Escherichia coli by C567, C8, and C9.
J Infect Dis. 1974 Apr;129(4):444-50
PMID: 4206245
-
Reaction mechanisms of nascent C567 (reactive lysis). I. Reaction characteristics for production of EC567 and lysis by C8 and C9.
J Immunol. 1972 Aug;109(2):353-9
PMID: 4558539
-
Ion transport across thin lipid membranes: a critical discussion of mechanisms in selected systems.
Q Rev Biophys. 1972 May;5(2):187-282
PMID: 4559448
-
The complement system.
Sci Am. 1973 Nov;229(5):54-66
PMID: 4748119
-
Studies of guinea pig complement component C9: reaction kinetics and evidence that lysis of EAC1-8 results from a single membrane lesion caused by one molecule of C9.
J Immunol. 1973 Mar;110(3):637-47
PMID: 4688916
-
Molecular analysis of the membrane attack mechanism of complement.
J Exp Med. 1972 Mar 1;135(3):549-66
PMID: 5058233
-
Voltage-dependent conductance induced in thin lipid membranes by monazomycin.
J Gen Physiol. 1972 Sep;60(3):263-84
PMID: 5055789
-
Further evidence for immune cytolysis by antibody and the first eight components of complement in the absence of C9.
Immunology. 1972 Jan;22(1):131-40
PMID: 5013908
-
The unit conductance channel of alamethicin.
Biochim Biophys Acta. 1972 Mar 17;255(3):1014-8
PMID: 5020218
-
Molecular aspects of polyene- and sterol-dependent pore formation in thin lipid membranes.
J Gen Physiol. 1970 Mar;55(3):375-400
PMID: 4938534
-
On the mechanism of cytolysis by complement: evidence on insertion of C5b and C7 subunits of the C5b,6,7 complex into phospholipid bilayers of erythrocyte membranes.
Proc Natl Acad Sci U S A. 1975 Dec;72(12):5076-80
PMID: 1061092
-
Chromatography of proteins on diethylaminoethyl-cellulose in concentrated ammonium sulfate.
Anal Biochem. 1971 Jun;41(2):466-70
PMID: 5104715
-
Complement-mediated lysis of liposomes produced by the reactive lysis procedure.
Immunology. 1970 Dec;19(6):983-6
PMID: 5530596
-
Lysis of erythrocytes by complement in the absence of antibody.
J Exp Med. 1970 Nov;132(5):898-915
PMID: 5470509
-
Mechanism of alkali cation transport in bulk membranes using macrotetrolide antibiotics.
Biochem Biophys Res Commun. 1969 Aug 7;36(3):387-93
PMID: 5822396
-
Resistance changes in lipid bilayers: immunological applications.
Science. 1968 Jun 7;160(3832):1119-21
PMID: 5647433