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

Goodrum, K J

doi:10.1128/iai.55.5.1101-1105.1987

Cited by 10 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, addition of latex beads in the same way resulted in a C3 concentration of 5.6 ng/ml. This lack of a stimulatory effect is in agreement with previous reports (16,29).…”

Section: Methodssupporting

confidence: 94%

See 1 more Smart Citation

Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor

Høgåsen

Abrahamsen

1993

Infect Immun

View full text Add to dashboard Cite

Activation of the complement system is an important part of host resistance against fungal infections. When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found. However, when C. albicans was administered to freshly isolated monocytes, a consistent stimulation of factor B biosynthesis occurred, while the C3 production was increased in about 50%o of the donors. C. albicans also induced the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the cultured cells, apparently in larger amounts in the donors in whom no stimulation of C3 production was found. An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 production. Furthermore, when monocytes were treated with recombinant human GM-CSF either at the same time as or 4 days prior to the addition of C. albicans, the increase in C3 production was suppressed or neutralized, while factor B biosynthesis was unaffected. Taken together, these results indicate that monocytes respond to C. albicans with an increased production of complement factors. This may be an important mechanism both for opsonization of the fungus and for initiation of an inflammatory reaction. At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF.Candida albicans is an opportunistic pathogen which may cause severe disseminated disease in immunocompromised patients (32). The host defense against fungal infections is accomplished by phagocytes, including monocytes/macrophages, in addition to cell-mediated and humoral immune mechanisms (36). Opsonization of C. albicans by complement factors and immunoglobulins enhances phagocytosis and intracellular killing of the yeast by the phagocytes (33). Monocytes/macrophages are the main extrahepatic source of complement factors (6, 20, 22, 41), and they provide all the components necessary for local complement activation. Factor B, the initial component of the alternative pathway, is activated after direct contact with microorganisms and other foreign agents. C3 is a key component in the complement system, as it represents a joining site for the classical and alternative pathways to a common terminal pathway. The cleavage products obtained during complement activation are potent anaphylatoxins, chemotaxins, and opsonins, which are important in the local inflammatory reaction (19).The monocyte production of complement factors is modulated by several physiological and foreign substances, such as interferons (18), immuncomplexes (27), and lipopolysaccharide (LPS) (38, 39). The ingestion of streptococci has been shown to stimulate C3 production in macrophage-like cell lines (16). Phagocytosis may stimulate the monocytes/ * Corresponding author. Electronic mail address: a.k.hogasen@ rh.uio.no(INTERNET).

show abstract

“…On the other hand, addition of latex beads in the same way resulted in a C3 concentration of 5.6 ng/ml. This lack of a stimulatory effect is in agreement with previous reports (16,29).…”

Section: Methodssupporting

confidence: 94%

“…Stimulation of C3 biosynthesis has been reported in mouse macrophage-like cell lines after treatment with whole, heatkilled streptococci, while latex beads were ineffective (16).…”

Section: Discussionmentioning

confidence: 99%

Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor

Høgåsen

Abrahamsen

1993

Infect Immun

View full text Add to dashboard Cite

show abstract

“…In the present study we analyzed the entry and subsequent survival of nonopsonized and opsonized GBS in macrophages. For this we used the well-established macrophage-like mouse cell line J774, which has features similar to those of normal macrophages and has frequently been used in functional studies on the phagocytosis of GBS (16,17,28).…”

Section: Discussionmentioning

confidence: 99%

Entry and intracellular survival of group B streptococci in J774 macrophages

et al. 1996

View full text Add to dashboard Cite

The mouse macrophage-like cell line J774 was used to analyze opsonin-independent entry and survival of group B streptococci (GBS). Efficient entry of GBS in J774 cells occurred within 5 min postinfection, and streptococci persisted intracellularly without loss of viability for at least 8 h. At 24 h postinfection, 30% of the total intracellular GBS was recovered from macrophages. Inhibition studies using different biochemical modulators of cellular functions showed that bacterial entry seemed to involve nonglycosylated J774 surface structures different from known receptors such as fibronectin-binding integrins. Internalization of GBS by J774 cells occurred by a microfilament-dependent phagocytosis-like process also involving participation of receptor-mediated endocytosis. Prior opsonization of GBS with human serum containing anti-GBS antibodies did not affect bacterial entry but significantly reduced the intracellular survival of GBS. Transmission electron microscopic analysis confirmed these findings and demonstrated that both opsonized and nonopsonized bacteria were contained within phagosomes during the whole infection period. Transmission electron microscopy further revealed that decreased intracellular survival rates of opsonized GBS appeared to be due to increased lysosomal activities of the macrophages. These results suggest that in the absence of opsonins, GBS are able to enter and persist efficiently in macrophages by evading intracellular antibacterial activities commonly associated with opsonin-mediated uptake.

show abstract

“…Phagocytosis of the nonencapsulated isolates might explain why they did not induce C3 secretion; however, C3 was secreted in response to phagocytized Candida albicans (data not shown). Goodrum (16) reported that stimulation of C3 from macrophages by group B streptococci could be inhibited by cytochalasin B but that this treatment did not inhibit induction of C3 by endotoxin. The phagocytic process per se was not sufficient to induce C3 from macrophages, since ingestion of latex beads did not induce C3.…”

Section: Discussionmentioning

confidence: 99%

“…ELISA for C3. An ELISA for murine C3 was developed as described by Goodrum (16). Wells of 96-well, flat-bottom microtiter plates (Immulon IV) were coated with 0.1 ml of a 1:750 dilution of goat anti-mouse C3 (Cooper Biomedical) diluted in coating buffer (0.1 M NaHCO 3 ; pH 8.2).…”

Section: Methodsmentioning

confidence: 99%

Secretion of the C3 component of complement by peritoneal cells cultured with encapsulated Cryptococcus neoformans

Blackstock

Murphy

1997

Infect Immun

View full text Add to dashboard Cite

Two isolates of Cryptococcus neoformans were identified as being widely divergent in pathogenic potential after intratracheal infection of mice. These isolates differed in their ability to upregulate capsule synthesis when grown under tissue culture conditions, and this property correlated with virulence. We postulated that differential capsule synthesis may cause differential stimulation of macrophages to produce products such as complement components. To test this hypothesis, heat-killed yeast cells were incubated with normal mouse peritoneal cells (PC) before the level of C3 secreted was determined. Cryptococcal stimulants were grown on mycological agar, which does not promote capsule synthesis, or in RPMI 1640 at 37°C in an atmosphere of 5% CO 2 , which stimulates capsule synthesis, to determine the role that the capsule plays in the induction of C3 secretion. C3 levels were elevated in cultures containing cryptococci grown in RPMI 1640 at 37°C in an atmosphere of 5% CO 2 , and the level of C3 detected was correlated with the amount of capsule expressed by the yeast cell stimulant. Nonencapsulated mutants of C. neoformans did not stimulate C3 secretion. Purified capsular polysaccharide (glucuronoxylomannan [GXM]) also stimulated the PC to secrete C3. Two signals were required before GXM stimulated C3 secretion. The second signal was identified as endotoxin present in small amounts (0.06 ng per ml) in tissue medium. Endotoxin may provide a priming stimulus for PC to express receptors or other cytokines needed for effective stimulation of C3. These experiments show that enhancement of C3 secretion by C. neoformans is due to GXM and is correlated with the virulence of the cryptococcal isolate.

show abstract

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

Cited by 10 publications

References 31 publications

Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor

Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor

Entry and intracellular survival of group B streptococci in J774 macrophages

Secretion of the C3 component of complement by peritoneal cells cultured with encapsulated Cryptococcus neoformans

Contact Info

Product

Resources

About