Production of C3 as a marker of lymphokine-mediated macrophage activation

Koestler, Thomas P.; Kirsh, Richard; Kline, Thomas; Rieman, David J.; Greig, Russell; Poste, George

doi:10.1016/0008-8749(84)90125-4

Cited by 11 publications

(5 citation statements)

References 35 publications

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“…A plateau (162 ng of C3/24 h per 106 cells) was reached on day 6 or 7, when harvesting the whole medium every 24 h, and evidence for synthesis de novo was provided by cycloheximide inhibition and recovery of C3 production after removal of the inhibitor. Kinetic study showed that, after being differentiated into macrophages (up to 4 days of culture in the presence of PMA), the U-937 cells synthesized increasing amounts of C3 only for 6 h. The cumulative C3 production in the medium reached a plateau of 160 ng of C3/ 106 cells in 6 h, and remained stable over 48 h. This synthesis is rather higher than that described for Corynebacterium parvumstimulated guinea-pig peritoneal macrophages (180 ng/ 12 h per 106 cells) (Zimmer et al, 1982), and lower than that recently reported for murine macrophages exposed to lymphokines containing macrophage-activating factor (44 ng/12 h per 105 cells) (Koestler et al, 1984). When the culture medium was not changed, the amount of C3 remained stable for 6-48 h. These observations could indicate that C3 exerts a feedback effect on C3 synthesis; such a mechanism was observed for C4 synthesis by guinea-pig peritoneal macrophages (Auerbach et al, 1984).…”

Section: Discussioncontrasting

confidence: 52%

“…The cells of the monocyte/macrophage lineage are known to produce complement components. Monocytes and macrophages can synthesize Cl (Muller et al, 1978;Bensa et al, 1985), C2 (Einstein et al, 1976;Beatty et al, 1981), C3 (Whaley, 1980;Strunk et al, 1983;Koestler et al, 1984), C4 (Lai et al, 1975;Colten, 1982), C5 (Hartung & Hadding, 1983) and all the components of the alternative pathway (Whaley, 1980;Hartung & Hadding, 1983;Ezekowitz et al, 1983). C2 and C4 biosynthesis has been extensively studied, but fewer data are available for C3, especially concerning its structural form and kinetics of synthesis.…”

Section: Introductionmentioning

confidence: 99%

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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

Bengio¹,

Gilbert²,

Peulve³

et al. 1986

Biochemical Journal

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Phorbol myristate acetate (PMA)-stimulated human monocyte-like cells (U-937) were found to synthesize the third component of complement (C3), as shown by enzyme-linked immunosorbent assay and immunoprecipitation from [35S]methionine-labelled culture supernatants. C3 synthesis occurred at a rate of about 160 ng of C3/24 h per 10(6) cells on day 7 after addition of PMA; it was blocked by cycloheximide treatment and was restored after removal of the inhibitor. SDS/polyacrylamide-gel-electrophoretic analysis of the immunoprecipitated protein showed that the size and subunit structure of the newly synthesized C3 were identical with those of plasma C3, and that a single-chain intracellular precursor was present in the cell lysates. Haemolytic assays showed that the synthesized C3 fully expressed functional activity in early culture within 4 h. After longer culture, a loss of haemolytic activity was observed. The possibility that newly secreted C3 is cleaved by U-937 cells themselves was suggested.

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Section: Discussioncontrasting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

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

Bengio¹,

Gilbert²,

Peulve³

et al. 1986

Biochemical Journal

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“…Stimulation of local C3 levels by GBS or other persistent bacterial antigens at sites of inflammation may potentiate the inflammatory reaction. C3 is synthesized and secreted by monocytes and macrophages constitutively (5,6,23), and enhanced C3 synthesis has been reported in macrophages "activated" by various particulate and soluble stimuli including lymphokine-rich lymphocyte culture supernatant fluids (17), gamma interferon (23), LPS (20,35), and Corynebacterium parvum (38). Koestler et al.…”

Section: Discussionmentioning

confidence: 99%

“…Koestler et al. (17) demonstrated that enhanced C3 synthesis in macrophages correlated with their activation to tumoricidal function. Enhanced extracellular C3 in activated macrophages, including PCW-stimulated macrophages (Goodrum, in press), is due to increased synthesis (23,35) as shown by cycloheximide-inhibitable changes in C3 levels.…”

Section: Discussionmentioning

confidence: 99%

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Stimulation of complement component C3 synthesis in macrophagelike cell lines by group B streptococci

Goodrum¹

1987

Infect Immun

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Complement levels and complement activation are key determinants in streptococcus-induced inflammatory responses. Activation of macrophage functions, such as complement synthesis, by group B streptococci (GBS) was examined as a possible component of GBS-induced chronic inflammation. Using an enzyme-linked immunosorbent assay, secreted C3 from mouse macrophagelike cell lines (PU5-1.8 and J774A.1) was monitored after cultivation with GBS. Whole, heat-killed GBS (1 to 10 CFU per macrophage) of both type Ia and III strains induced 25 to 300% increases in secreted C3 in both cell lines after a 24-h cultivation. GBS-treated cell lines exhibited increases in secreted lysozyme (10%) and in cellular protein (25 to 50%). Inhibition of macrophage phagocytosis by cytochalasin B inhibited GBS stimulation of C3. Purified cell walls of GBS type m strain 603-79 (1 to 10 ,ug/ml) also enhanced C3 synthesis. Local enhancement of macrophage C3 production by ingested streptococci or by persistent cell wall antigens may serve to promote chronic inflammatory responses.

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Modifications Induced by Activation to Tumor Cytotoxicity in the Protein Secretory Activity of Macrophages

Grand-Perret

Petit

Lemaire

1986

Journal of Leukocyte Biology

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After biosynthetic radiolabeling, polypeptides secreted by macrophages were analyzed by electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate and fluorography. Comparative studies of various macrophage populations (inflammatory macrophages, primed and activated macrophages, resident macrophages) showed that secretory activity is elaborately controlled according to macrophage developmental and functional state. When young macrophages activated to cytotoxicity against tumor cells by an appropriate eliciting agent and culture in the presence of lipopolysaccharide were compared to mature resident macrophages devoid of antitumor activity, the following changes were observed in the protein secretion phenotype: (1) New polypeptides are expressed: the intensity of four bands was increased more than five-fold on one-dimensional gels and 17 new spots were detected on two-dimensional gels. (2) The production of several major polypeptides is repressed: six bands were strongly decreased on one-dimensional gels, and 11 major spots (or groups of spots) were lost on two-dimensional gels. (3) The charge microheterogeneity pattern exhibited by several polypeptides on two-dimensional gels is shifted towards less acidic species.

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Production of C3 as a marker of lymphokine-mediated macrophage activation

Cited by 11 publications

References 35 publications

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

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

Stimulation of complement component C3 synthesis in macrophagelike cell lines by group B streptococci

Modifications Induced by Activation to Tumor Cytotoxicity in the Protein Secretory Activity of Macrophages

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