Biosynthesis of the third component of complement (C3) by the human monocytic-cell line U-937 Induction by phorbol myristate acetate

Bengio, S; Gilbert, Danièle; Peulve, Pascal; Daveau, Maryvonne; Fontaine, Marc

doi:10.1042/bj2390711

Cited by 12 publications

(8 citation statements)

References 38 publications

(46 reference statements)

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“…However, after 24 h of incubation the proportion of intact C3 was lower than after 2 h (results not shown). This is in agreement with the results of Bengio et al [10], who observed that the haemolytic activity of U937-derived C3 decreased after 6 h in culture due to proteolysis.…”

Section: Modulation Of Synthesis and Phosphorylation Of C3 In Vitrosupporting

confidence: 93%

“…Complement components are mostly synthesized in hepatocytes [1][2][3][4], but substantial amounts are also secreted by monocytes\macrophages [5][6][7] ; local synthesis of complement proteins by macrophages plays an important role in the inflammatory response [8]. The human monocytic cell line U937 [9] is a suitable model for complement synthesis in monocytes\ macrophages, and has been reported to synthesize a number of components, including C3 [10], C4 [11], Factor B [12] and Factor H [13]. The secretion of C3 by U937 is stimulated by, e.g., PMA, [10,14], lipopolysaccharide (LPS), and interferon-γ [11].…”

Section: Introductionmentioning

confidence: 99%

“…The human monocytic cell line U937 [9] is a suitable model for complement synthesis in monocytes\ macrophages, and has been reported to synthesize a number of components, including C3 [10], C4 [11], Factor B [12] and Factor H [13]. The secretion of C3 by U937 is stimulated by, e.g., PMA, [10,14], lipopolysaccharide (LPS), and interferon-γ [11].…”

Section: Introductionmentioning

confidence: 99%

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Phosphorylation of complement component C3 after synthesis in U937 cells by a putative protein kinase, casein kinase 2, which is regulated by CD11b: evidence that membrane-bound proteases preferentially cleave phosphorylated C3

Ekdahl

Nilsson

1997

Biochemical Journal

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It was our aim in this study to investigate the possibility that the third component of complement (C3) is phosphorylated during synthesis and secretion in U937 cells. Labelling of U937 cells with [32P]Pi, followed by immunoprecipitation of C3 from cell lysates and culture supernatants at different time points, showed that C3 was phosphorylated intracellularly immediately before release into the medium, which initiated cleavage of the protein into an iC3b-like fragment. Stimulation of CD11b/CD18 increased phosphorylation 7-fold, from a basal level of 2%. The phosphorylation sites in C3 did not resemble those described previously for casein kinase (CK) 1, cAMP-dependent protein kinase A or calcium- and phospholipid-dependent protein kinase C. Instead, protein kinase CK2 was suggested inasmuch as: (1) CK2 was detected both on the cell surface and on shed microparticles; (2) phosphorylation of purified C3 by microparticles was abolished by a monoclonal antibody, anti-CK2; (3) the [32P]Pi tag of both phosphorylated C3 (secreted from U937 cells) and of microparticle-phosphorylated C3, which was cleaved either by membrane proteases or by leucocyte elastase, was found in a 40 and a 70 kDa polypeptide; (4) both secreted C3 and C3 phosphorylated in vitro were much more susceptible to cleavage by proteases. Generation of C3 fragments provides a means by which U937 cells can stimulate nearby cells which are expressing complement receptors. The present study demonstrates that the cleavage of C3 is controlled by an intracellular phosphorylation event regulated by CD11b/CD18.

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Section: Modulation Of Synthesis and Phosphorylation Of C3 In Vitrosupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phosphorylation of complement component C3 after synthesis in U937 cells by a putative protein kinase, casein kinase 2, which is regulated by CD11b: evidence that membrane-bound proteases preferentially cleave phosphorylated C3

Ekdahl

Nilsson

1997

Biochemical Journal

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“…It has been shown by several groups that activation of M ¤ enhances C3 production, and locally produced C3 is known to influence several cellular responses [14][15][16][17][18][19]. We found that M ¤ cultured on immobilized C1q and MBL also produced increased amounts of C3 (measured by ELISA) and C1q proved to be a more potent activator (data not shown).…”

Section: Self Opsonization By C3 Derived From C1qand Mbl-stimulated M Dmentioning

confidence: 55%

Mannan-binding lectin and C1q bind to distinct structures and exert differential effects on macrophages

et al. 2000

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While the interaction of complement component C1q with cellular proteins is extensively studied, much less is known about the binding of the structurally related molecule, mannan‐binding lectin (MBL) to various cells. Here we show by cytofluorimetry that the interaction of MBL with immunocompetent cells is much more restricted than that of C1q. It is shown that under conditions of physiological ionic strength MBL binds to human monocyte‐derived macrophages (Mϕ) and monocytoid cell lines, but not to T and B lymphocytes, in contrast to C1q, which interacts with all these cells under the same conditions. As opposed to the binding of C1q, low ionic strength does not improve the interaction of MBL with Mϕ. No competition for cellular binding sites was found when MBL and C1q were added simultaneously to the cells. Studying the functional consequences of the interaction, we found that the release of TNF‐α from Mϕ is induced by C1q but not by MBL. Production of complement C3 by Mϕ is stimulated by C1q strongly, while the effect of MBL is much weaker. C3 produced upon C1q‐mediated triggering is shown to opsonize RBC, resulting in enhanced phagocytosis. These results suggest that cell membrane molecules binding MBL and C1q are not identical; moreover, biological functions exerted by these proteins are also markedly different.

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“…Thccostimulaiory effect of certain IgG isotypes and lL-6 on C3 biosynthesis by macrophages, and the actual expression and availability of FcvRs, may have an important role in local immune responses. All the more since C3 produced by macrophages has been demonstrated to be cleaved by cell surface proteases, to bind covalently to the C3-producing cell [16,21,22] and to modulate various FcyR-dependent functions [22]. In addition.…”

Section: Discussionmentioning

confidence: 99%

FcγR‐Dependent Regulation of the Biosynthesis of Complement C3 by Murine Macrophages: the Modulatory Effect of IL‐6

Bajtay¹,

Falus²,

Erdei³

et al. 1992

Scand J Immunol

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The effect of murine IgG isotypes on the gene expression and secretion of the third component of complement (C3) has been studied using the monocytoid cell line P388D1 and oil-elicited mouse peritoneal macrophages. It is demonstrated that the binding of IgG2a and IgG2b but not IgG1 and IgG3 augments the biosynthesis of C3 both in the presence and in the absence of the phorbol ester, phorbol myristate acetate in the case of both cell types. The multifunctional cytokine interleukin-6 (IL-6) alone reveals no effect on the gene expression of C3, but increases the effectiveness of mouse IgG2a and IgG2b. Confirming the role of Fc gamma RII, a strong up-regulation of C3 gene expression and C3 secretion was found when macrophages were cultured with the F(ab')2 fragment of the Fc gamma RII-specific monoclonal antibody 2.4G2.

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Biosynthesis of the third component of complement (C3) by the human monocytic-cell line U-937 Induction by phorbol myristate acetate

Cited by 12 publications

References 38 publications

Phosphorylation of complement component C3 after synthesis in U937 cells by a putative protein kinase, casein kinase 2, which is regulated by CD11b: evidence that membrane-bound proteases preferentially cleave phosphorylated C3

Phosphorylation of complement component C3 after synthesis in U937 cells by a putative protein kinase, casein kinase 2, which is regulated by CD11b: evidence that membrane-bound proteases preferentially cleave phosphorylated C3

Mannan-binding lectin and C1q bind to distinct structures and exert differential effects on macrophages

FcγR‐Dependent Regulation of the Biosynthesis of Complement C3 by Murine Macrophages: the Modulatory Effect of IL‐6

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