Channel fluctuations induced by membrane attack complex C5b-9

Young, John Ding‐E; Young, Tsen Men

doi:10.1016/0161-5890(90)90123-h

Cited by 16 publications

(6 citation statements)

References 17 publications

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“…An alternative hypothesis is that of Esser, who has suggested a 'leaky patch' formation in the vicinity of MAC [3]. However, Esser's group has recently published data showing the formation of single channels by MAC in artificial bilayer membranes [4], data which support other recent work showing single channel formation by MAC [5,6]. These studies have indicated that there is selectivity for cations over anions upon formation of the channel.…”

Section: Introductionmentioning

confidence: 83%

Complement-induced Ca2+ influx in cultured fibroblasts is decreased by the calcium-channel antagonist nifedipine or by some bivalent inorganic cations

Newsholme

Adogu

Soos

et al. 1993

Biochemical Journal

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The effects of different extracellular cations or organic Ca(2+)-channel modulators on complement-induced changes in intracellular Ca2+ and cell death have been investigated in the transfected NIH-3T3 HIR 3.5 cell line, which overexpresses the human insulin receptor. Cells were incubated with mouse anti-(human insulin receptor) monoclonal antibodies before exposure to rabbit or human serum (sources of heterologous complement). Changes in intracellular Ca2+ were complement-dependent (measured by influx of 45Ca), as was cytotoxicity (monitored by leakage of lactate dehydrogenase into the culture supernatant). Addition of a dihydropyridine Ca(2+)-channel antagonist (nifedipine) or some bivalent inorganic cations caused inhibition of 45Ca entry via a novel channel distinct from endogenous voltage-gated Ca2+ channels. Nifedipine decreased, but conversely the addition of a phenylalkylamine Ca(2+)-channel antagonist (verapamil) or the inorganic Ca2+ agonists Ba2+ and Sr+ increased, complement-induced cytotoxicity. These agents had no effect on cell viability at the studied concentrations, in the absence of complement. It is concluded that complement-induced cytotoxicity is mediated by Ca2+ influx through novel specific transmembrane channels which are sensitive to the Ca(2+)-channel antagonist nifedipine, but otherwise show little resemblance to L- or T-type voltage-gated Ca2+ channels.

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Section: Introductionmentioning

confidence: 83%

Complement-induced Ca2+ influx in cultured fibroblasts is decreased by the calcium-channel antagonist nifedipine or by some bivalent inorganic cations

Newsholme

Adogu

Soos

et al. 1993

Biochemical Journal

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“…This term is often considered synonymous with the distinct proteinlined pore structure, first described in electron micrographs of complement lysed targets in the mid-1960s 9,10 ; however, a considerable body of evidence demonstrates that functional, membrane-disrupting MAC can be formed in the absence of detectable pores. [11][12][13] Indeed, an entertaining debate pervaded the 1980s between those who contended that membrane attack, detergent-like, induced "leaky patches" in membranes and those who considered the pore to be the lytic lesion. 14,15 As is often the case, both "leak-ers" and pore-ers" were right in some respects.…”

Section: The Membrane Attack Complex-structural Historymentioning

confidence: 99%

Terminal complexes of the complement system: new structural insights and their relevance to function

Morgan

Walters

Serna

et al. 2016

Immunological Reviews

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Structure-function in membrane attack. SummaryComplement is a key component of innate immunity in health and a powerful driver of inflammation and tissue injury in disease. The biological and pathological effects of complement activation are mediated by activation products. These come in two flavours: i) proteolytic fragments of complement proteins (C3, C4, C5) generated during activation that bind specific receptors on target cells to mediate effects; ii) the multimolecular membrane attack complex generated from the five terminal complement proteins that directly binds to and penetrates target cell membranes. Several recent publications have described structural insights that have changed perceptions of the nature of this membrane attack complex. This review will describe these recent advances in understanding of the structure of the membrane attack complex and its by-product the fluid-phase terminal complement complex and relate these new structural insights to functional consequences and cell responses to complement membrane attack.

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“…In these investigations, the complement system has been activated by the addition of C5b-6 (reactive lysis), [55][56][57][58] after the addition of antigen and antibody, 53,60 or the adsorption of antibodies onto the membranes. 59 In all cases, an increase in membrane conductance has been observed.…”

Section: Complementmentioning

confidence: 99%

“…In the literature, only few investigations into the conductance changes induced by complement as measured in symmetric planar phospholipid bilayers [51][52][53][54][55][56][57][58] as well as in patch-clamped cells 59 have been reported, and the results of these studies concerning pore size, its stability, and also the requirements of complement components for the induction of conductance changes differ considerably. In these investigations, the complement system has been activated by the addition of C5b-6 (reactive lysis), [55][56][57][58] after the addition of antigen and antibody, 53,60 or the adsorption of antibodies onto the membranes. 59 In all cases, an increase in membrane conductance has been observed.…”

Section: Complementmentioning

confidence: 99%

Review: Towards antibacterial strategies: studies on the mechanisms of interaction between antibacterial peptides and model membranes

Wiese

Gutsmann

Seydel

2003

Journal of Endotoxin Research

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Lipopolysaccharides (LPSs) play a dual role as inflammation-inducing and as membrane-forming molecules. The former role attracts significantly more attention from scientists, possibly because it is more closely related to sepsis and septic shock. This review aims to focus the reader's attention to the other role, the function of LPS as the major constituent of the outer layer of the outer membrane of Gram-negative bacteria, in particular those of enterobacterial strains. In this function, LPS is a necessary component of the cell envelope and guarantees survival of the bacterial organism. At the same time, it represents the first target for attacking molecules which may either be synthesized by the host's innate or adaptive immune system or administered to the human body. The interaction of these molecules with the outer membrane may not only directly cause the death of the bacterial organism, but may also lead to the release of LPS into the circulation. Here, we review membrane model systems and their application for the study of molecular mechanisms of interaction of peptides such as those of the human complement system, the bactericidal/permeability-increasing protein (BPI), cationic antibacterial peptide 18 kDa (CAP18) as an example of cathelicidins, defensins, and polymyxin B (PMB). Emphasis is on electrical measurements with a reconstitution system of the lipid matrix of the outer membrane which was established in the authors' laboratory as a planar asymmetric bilayer with one leaflet being composed solely of LPS and the other of the natural phospholipid mixture. The main conclusion, which can be drawn from these investigations, is that LPS and in general its negative charges are the dominant determinants for specific peptide-membrane interactions. However, the detailed mechanisms of interaction, which finally lead to bacterial killing, may involve further steps and differ for different antibacterial peptides.

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Channel fluctuations induced by membrane attack complex C5b-9

Cited by 16 publications

References 17 publications

Complement-induced Ca2+ influx in cultured fibroblasts is decreased by the calcium-channel antagonist nifedipine or by some bivalent inorganic cations

Complement-induced Ca2+ influx in cultured fibroblasts is decreased by the calcium-channel antagonist nifedipine or by some bivalent inorganic cations

Terminal complexes of the complement system: new structural insights and their relevance to function

Review: Towards antibacterial strategies: studies on the mechanisms of interaction between antibacterial peptides and model membranes

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