Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide.

Strunk, Robert C.; Whitehead, Alexander S.; Cole, F S

doi:10.1172/jci112099

Cited by 89 publications

(49 citation statements)

References 43 publications

(25 reference statements)

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“…The extracellular C3 was characterized by a band of ^ 185 kD corresponding to pro-C3 [17] and bands of ^112 kDand 72 kD corresponding to the x-and /i-potypeptidc chains. These were detected at a siinilar level in the culture fluid of both control-and lFN-y-stimulated GMC (Fig.…”

Section: Biosynthesis Of C3 and C4 Proteins By Gmcmentioning

confidence: 99%

C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells

Sacks

Zhou

Campbell³

et al. 1993

Clinical and Experimental Immunology

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SUMMARYThe glomerular mesangial cell (GMC) plays a key role in ihe maintenance of glomerular structure and function and in the mediation of glomerular injury. To explore the potential of lUis cell to produee complement and react to local inflammatory signals, we studied the synthesis and regulation of the third and fourth eomponents of complement in cultured human GMC. Using metabolic labelling and immunoprecipitalion, we found that C3 and C4 polypeptide chains were synthesized and secreted by GMC, Interferon-gamma (IFN-y) led loan increase inC4 protein synthesis, but not C3 synthesis. There was a eorresponding increase in C4 mRNA in lEN-y-activaled cells, but no increase in C3 mRNA. as determined by semi-quantitative polymerase chain reaction (PCR) estimation. These results demonstrate thai human GMC can synthesize C3 and C4 proteins, and ihat regulation of expression of the C4 gene is mediated by IFN-/. We hypothesize that GMC production of complement could influenee the clearance of immune aggregates by the kidney and the mediation of glomerular injury.

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Section: Biosynthesis Of C3 and C4 Proteins By Gmcmentioning

confidence: 99%

C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells

Sacks

Zhou

Campbell³

et al. 1993

Clinical and Experimental Immunology

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“…Immediately after the adherence periods, the cells were washed to remove conditioned medium and cultured for 2 h in 1.0 ml methionine-free medium containing 500 uCi [35S]methionine (24,25), except that the labeling medium contained protease inhibitors (10% dialyzed heat-inactivated FCS, 1 mg/ml soybean trypsin inhibitor, and 100…”

Section: Biosynthetic Labeling and Immunoprecipitationmentioning

confidence: 99%

“…C5 was always the first antigen precipitated to avoid possible interference of residual C3-anti-C3 complexes with the C5 signal. Incorporation of [35S]methionine into individual immunoprecipitated proteins was determined in gel slices after digestion with 15% hydrogen peroxide for 16 h and addition of ScintiVerse II (Fisher Scientific Co., Fair Lawn, NJ) (24,25); the radioactivity in the gel slices was adjusted for the amount of total protein synthesized under the specific conditions, as determined by precipitation of aliquots of the lysates with 10% TCA (25). Preliminary experiments demonstrated that incorporation of [35S]methionine into both total protein and specific complement proteins was dependent upon concentration of radiolabeled amino acid from 100 to 900 MCi/ml and was linear with time of culture up to 2 h.…”

Section: Biosynthetic Labeling and Immunoprecipitationmentioning

confidence: 99%

Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways.

Strunk¹,

Eidlen²,

Mason³

1988

J. Clin. Invest.

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262

137

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The serum complement system is a major mediator of inflammation reactions. Two of the complement proteins, the third (C3) and fifth (C5) components, are precursors of potent phlogistic molecules, C3a and CSa. C5a has potent chemotactic activity and plays an active role in pulmonary inflammation. We present evidence suggesting that several complement proteins, including C5, are synthesized locally in the lung in alveolar type II epithelial cells. Lung tissue from normal mice synthesized and secreted C5 protein similar to the C5 protein in mouse serum, whereas lung tissue from C5-deficient mice did not. Lung tissues from both normal and C5-deficient mice synthesized C3. Rat lung tissue synthesized and secreted C5, as well as C2, C4, C3, and factor B. Cultures of type II cells (95% type II cells, 5% macrophages) regularly synthesized all these proteins. In contrast, cultures of macrophages alone synthesized large amounts of C2 and factor B, and in some experiments C3 and C4, but never C5. The C5 synthesized by the rat cells was slightly larger than serum C5 (200 kD compared with 180 kD) and was not processed to the two-chain molecule seen in serum. Rat lung tissue and purified type II cells contained C5 mRNA with the same molecular mass as the C5 mRNA in rat liver and in mouse lung and liver. Human type II cells also synthesized C5, as well as C2, C4, C3, and factor B. Human pulmonary macrophages synthesized only C2, factor B, and, in some experiments, C3. Synthesis of complement proteins in cells that line the alveolar wall may provide a local source of these proteins for inflammatory responses in the lung. Local synthesis of complement proteins could be regulated independently of the synthesis in the liver.

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“…IL-1␤ and TNF␣ are the main positive regulators of C3 expression during acute response in hepatocytes (9,10). C3 expression was also shown to be activated by inflammatory stimuli in tissue macrophages and the amplitude of the response in terms of the level of C3 gene activation is significantly higher (5-30-fold) in those cells than in hepatocytes (11)(12)(13). Nevertheless, the mechanism of C3 gene up-regulation in the liver and macrophages by proinflammatory cytokines is not elucidated enough.…”

mentioning

confidence: 99%

Peroxisome Proliferator-activated Receptor α Positively Regulates Complement C3 Expression but Inhibits Tumor Necrosis Factor α-mediated Activation of C3 Gene in Mammalian Hepatic-derived Cells

Mogilenko

Кудрявцев

Shavva

et al. 2013

Journal of Biological Chemistry

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Background: Expression and secretion of complement C3 is positively regulated in hepatocytes during acute inflammation. Results: Activation of PPAR␣ stimulates C3 expression but interferes with up-regulation of C3 gene by TNF␣-NF-B axis. Conclusion:Interplays between PPAR␣ and TNF␣ may be involved in control of C3 gene expression and protein secretion during acute inflammation. Significance: Novel mechanism of PPAR␣-dependent regulation of C3 gene in the liver has been shown.

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Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide.

Abstract: The third component of complement (C3)

Cited by 89 publications

References 43 publications

C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells

C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells

Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways.

Peroxisome Proliferator-activated Receptor α Positively Regulates Complement C3 Expression but Inhibits Tumor Necrosis Factor α-mediated Activation of C3 Gene in Mammalian Hepatic-derived Cells

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