Increased hemolytic activity of the trypsin-cleaved ninth component of complement

Tschopp, Jürg; Amiguet, Patrick; Schäfer, Sylvie

doi:10.1016/0161-5890(86)90171-9

Cited by 8 publications

(4 citation statements)

References 18 publications

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“…Ishida et al (1982) showed in a careful study that only C9b is in contact with the lipid bilayer. C9 can be cleaved by trypsin (Tschopp et al, 1985b) into two fragments with apparent molecular masses of 53 and 20 kDa. The cleavage occurs within C9b.…”

Section: Resultsmentioning

confidence: 99%

The membrane attack complex of complement: lipid insertion of tubular and nontubular polymerized C9

Amiguet¹,

Brunner²,

Tschopp³

1985

Biochemistry

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The membrane-restricted photoactivatable carbene generator 3-(trifluoromethyl)-3-(m-[125I]-iodophenyl)diazirine [Brunner, J., & Semenza, G. (1981) Biochemistry 20, 7174-7182] was used to label the subunits of the membrane attack complex of complement (C5b-9). C5b-9 complexes either were assembled from serum on erythrocyte membranes or were reconstituted from purified components on liposomes. After irradiation, most of the probe is bound to C9 independent of the membrane system used, indicating that the wall of the transmembrane channel is predominantly composed of C9. No difference was observed whether polymerized C9 was in the tubular or nontubular form [Podack, E. R., & Tschopp, J. (1983) J. Biol. Chem. 257, 15204-15212], showing that tubule closure is not essential for successful lipid insertion. The same label distribution between the two forms of polymerized C9 was obtained by analyzing zinc-polymerized C9 in the absence of C5b-8. Since the photoreactive probe reacted with at least two distinct polypeptide segments within C9, lipid interaction does not occur via a single segment of hydrophobic amino acids.

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Section: Resultsmentioning

confidence: 99%

The membrane attack complex of complement: lipid insertion of tubular and nontubular polymerized C9

Amiguet¹,

Brunner²,

Tschopp³

1985

Biochemistry

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“…Across both time points, Bb appeared more abundant in WT mice compared with TLR2 À/À mice post NaIO 3 treatment ( Figures 5P and 5R, top panels). Zymogen C9 (70 kD) is proteolytically cleaved at a specific site to induce C9 polymerization (Tschopp et al, 1986). The 25 kD product, which is the carboxyl-terminal fragment of C9 capable of disturbing membrane potential, was found to a strikingly greater extent in the WT mice compared with the TLR2 À/À mice at both 1 day (Figures 5P and 5Q) and 3 days (Figures 5R and 5S) post NaIO 3 treatment.…”

Section: Oxidative Stress-induced Tlr2 Activation Drives Mac Formationmentioning

confidence: 99%

Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration

et al. 2020

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Graphical Abstract Highlights d TLR2 activates the alternative complement pathway d TLR2 signaling triggers sub-lytic MAC formation on retinal pigment epithelial cells d TLR2 deficiency reduces oxidative stress-induced C3 and MAC in the outer retina d TLR2 blockade protects photoreceptors and RPE from oxidative stress-induced cell death SUMMARY Retinal degeneration is a form of neurodegenerative disease and is the leading cause of vision loss globally. The Toll-like receptors (TLRs) are primary components of the innate immune system involved in signal transduction. Here we show that TLR2 induces complement factors C3 and CFB, the common and rate-limiting factors of the alternative pathway in both retinal pigment epithelial (RPE) cells and mononuclear phagocytes. Neutralization of TLR2 reduces opsonizing fragments of C3 in the outer retina and protects photoreceptor neurons from oxidative stress-induced degeneration. TLR2 deficiency also preserves tight junction expression and promotes RPE resistance to fragmentation. Finally, oxidative stress-induced formation of the terminal complement membrane attack complex and Iba1+ cell infiltration are strikingly inhibited in the TLR2-deficient retina. Our data directly implicate TLR2 as a mediator of retinal degeneration in response to oxidative stress and present TLR2 as a bridge between oxidative damage and complement-mediated retinal pathology.

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“…Moreover, ten lncNATs and their complementary genes encoding proteinases/peptidases were upregulated in the susceptible fish ( Figure 6C ). The list of the proteinases/peptidases (n = 9) includes trypsin-1, chymotrypsin A, carboxypeptidase B, dipeptidase 1, and aminopeptidase N. Previous studies revealed that proteolytic enzymes, such as trypsin-1, can promote the hemolytic activity ( 112 ). We also identified four upregulated lncNATs complementary to the DE E-selectin in the susceptible fish line.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide identification of antisense lncRNAs and their association with susceptibility to Flavobacterium psychrophilum in rainbow trout

Ali¹,

Salem²

2022

Front. Immunol.

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Eukaryotic genomes encode long noncoding natural antisense transcripts (lncNATs) that have been increasingly recognized as regulatory members of gene expression. Recently, we identified a few antisense transcripts correlating in expression with immune-related genes. However, a systematic genome-wide analysis of lncNATs in rainbow trout is lacking. This study used 134 RNA-Seq datasets from five different projects to identify antisense transcripts. A total of 13,503 lncNATs were identified genome-wide. About 75% of lncNATs showed multiple exons compared to 36.5% of the intergenic lncRNAs. RNA-Seq datasets from resistant, control, and susceptible rainbow trout genetic lines with significant differences in survival rate following Flavobacterium psychrophilum (Fp) infection were analyzed to investigate the potential role of the lncNATs during infection. Twenty-four pairwise comparisons between the different genetic lines, infectious status, and time points revealed 581 differentially expressed (DE) lncNATs and 179 differentially used exons (DUEs). Most of the DE lncNATs strongly and positively correlated in expression with their corresponding sense transcripts across 24 RNA-Seq datasets. LncNATs complementary to genes related to immunity, muscle contraction, proteolysis, and iron/heme metabolism were DE following infection. LncNATs complementary to hemolysis-related genes were DE in the resistant fish compared to susceptible fish on day 5 post-infection, suggesting enhanced clearance of free hemoglobin (Hb) and heme and increased erythropoiesis. LncNATs complementary to hepcidin, a master negative regulator of the plasma iron concentration, were the most downregulated lncNATs on day 5 of bacterial infection in the resistant fish. Ninety-four DE lncNAT, including five complementary to hepcidin, are located within 26 QTL regions previously identified in association with bacterial cold water disease (BCWD) in rainbow trout. Collectively, lncNATs are involved in the molecular architecture of fish immunity and should be further investigated for potential applications in genomic selection and genetic manipulation in aquaculture.

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Increased hemolytic activity of the trypsin-cleaved ninth component of complement

Cited by 8 publications

References 18 publications

The membrane attack complex of complement: lipid insertion of tubular and nontubular polymerized C9

The membrane attack complex of complement: lipid insertion of tubular and nontubular polymerized C9

Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration

Genome-wide identification of antisense lncRNAs and their association with susceptibility to Flavobacterium psychrophilum in rainbow trout

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