Analysis of complement factor H mRNA expression: dexamethasone and IFN-.gamma. increase the level of H in L cells

Muñoz‐Cánoves, Pura; Tack, Brian F.; Vik, D P

doi:10.1021/bi00452a002

Cited by 28 publications

(14 citation statements)

References 36 publications

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“…Although it had not been shown before in these cell types, the IFN-␥-mediated up-regulation that was observed here for HC and KC was not unexpected because this phenomenon had formerly been observed in HUVEC (Brooimans et al, 1989;Dauchel at al, 1990;Lappin et al, 1992;Ripoche et al, 1988b;Schlaf et al, 2001), in primary myoblasts and in two rhabdomyosarcoma cell lines (CRL 1558 and HTB 153) (Legoedec et al, 1995), in primary fibroblasts (Friese et al, 1999;Katz and Strunk, 1988;Lappin et al, 1992;Schwaeble et al, 1991), in fibroblast-like L cells (Munoz-Canoves et al, 1989), in monocytes (Lappin et al, 1992), in the murine liver cell line ϩ/ϩLi (Vik, 1996), and in the human Hep3b hepatoma cell line (Luo and Vik, 1999) and may therefore be a common feature. In the present study, the proinflammatory cytokines TNF-␣, IL-6, and IL-1␤ did not upregulate FH.…”

Section: Factor H In Primary Liversupporting

confidence: 63%

“…The primary site of synthesis of FH is the liver (Zipfel and Skerka, 1994). Extrahepatic cell types such as human umbilical vein endothelial cells (HUVEC) (Brooimans et al, 1989(Brooimans et al, , 1990Ripoche et al, 1988b), peripheral blood monocytes (Whaley, 1980), cells of the monocytemacrophage series (De Ceulaer et al, 1980), primary skin fibroblasts (Katz and Strunk, 1988), fibroblast-like L cells (Munoz-Canoves et al, 1989;Vik, 1999), primary myoblasts and rhabdomyosarcoma cell lines (Legoedec et al, 1995), glioma cell lines (Gasque et al, 1992), and glomerular mesangial cells (van den Dobbelsteen et al, 1994) have also been reported to express FH. These cell types may function as local sources of FH and thereby reduce tissue damage caused by local complement activation.…”

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confidence: 99%

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Constitutive Expression and Regulation of Rat Complement Factor H in Primary Cultures of Hepatocytes, Kupffer Cells, and Two Hepatoma Cell Lines

Schlaf

Beisel

Pollok-Kopp

et al. 2002

Laboratory Investigation

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SUMMARY:The 155-kd soluble complement regulator factor H (FH), which consists of 20 short consensus repeats, increases the affinity of complement factor I (FI) for C3b by about 15 times. In addition to its cofactor activity, it prevents factor B from binding to C3b and promotes the dissociation of the C3bBb complex. The primary site of synthesis of FH, as well as of FI, is the liver, but the cell types responsible for the hepatic synthesis of both factors have not yet been clearly identified. In contrast to FI-mRNA, which was detectable only in hepatocytes (HC), FH-specific mRNA was identified in both HC and Kupffer cells (KC). As calculated for equal amounts of mRNA isolated from both cell types, FH-specific mRNA was found to be nearly 10-fold higher in KC than in HC, leading to the conclusion that KC are an abundant source of FH. Of the investigated proinflammatory cytokines IL-6, TNF-␣, IL-1␤, and IFN-␥, only IFN-␥ up-regulated FH-specific mRNA up to 6-fold in both primary HC and KC. This was also demonstrable on the protein level. However, FH-specific mRNA was not inducible in the rat hepatoma cell line H4IIE, which did not express FH-specific mRNA and could not be up-regulated in FAO cells that constitutively expressed FH-specific mRNA. This demonstrates that transformed cell lines do not reflect FH regulation in isolated primary HC. In addition to IFN-␥, the endotoxin lipopolysaccharide (LPS) up-regulated FH-specific mRNA nearly 10-fold in KC after stimulation at concentrations of 10 or 1 ng/ml. In contrast, concentrations of up to 2 g LPS/ml did not show any effect on HC. Our data suggest that LPS does not regulate the expression of FH in HC. (Lab Invest 2002, 82:183-192).T he regulation of complement activation at the level of C3 and C4 is mediated by several receptors and soluble regulatory proteins. These include complement receptor 1 (CD35), complement receptor 2 (CD21), decay-accelerating factor (CD55), membrane cofactor protein (CD46), factor I (FI), and factor H (FH). These proteins, with the exception of FI, form the "regulators of complement activation" family (Hourcade et al, 1989). Their genes are closely linked on chromosome 1 in man and mouse. This illustrates that this region on the long arm of chromosome 1 in humans is analogous to that region in mice (Klickstein et al, 1985). The serine protease FI could be located to chromosome 4 in man (Goldberger et al, 1987) and to chromosome 3 in mouse (Minta et al, 1996).The potentially deleterious complement system is strictly regulated to prevent damage in the absence of pathologic situations Mulligan et al, 1992;Piddlesden et al, 1994;Smith et al, 1993). On some host cell surfaces, membrane-bound complement regulatory factors are expressed only at low levels. Thus, reduced protection against complement attack may be compensated by the soluble regulator FH, which has a critical role in complement inactivation in the fluid phase (Meri and Pangburn, 1990; Pangburn and Müller-Eberhardt, 1978) and acts in concert with FI. FH is a single-chain protein...

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Section: Factor H In Primary Liversupporting

confidence: 63%

mentioning

confidence: 99%

Constitutive Expression and Regulation of Rat Complement Factor H in Primary Cultures of Hepatocytes, Kupffer Cells, and Two Hepatoma Cell Lines

Schlaf

Beisel

Pollok-Kopp

et al. 2002

Laboratory Investigation

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“…fH, however, is also synthesized de novo at various sites in the body, including the lung (6), skin fibroblasts (16), kidney (23,29), spleen (23), thymus (23), endothelial cells (25), and synovial fluid (11), and by primary human cervical epithelial cells (8). The newly developed human fH transgenic rat model expresses fH from a chicken betaactin promoter, which could result in expression of this protein at sites that do not normally express fH.…”

Section: Figmentioning

confidence: 99%

Enhanced Bacteremia in Human Factor H Transgenic Rats Infected by Neisseria meningitidis

Vu¹,

Shaughnessy

Lewis

et al. 2012

Infect Immun

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Neisseria meningitidis binds the complement downregulating protein, factor H (fH), which enables the organism to evade host defenses. Two fH ligands, fHbp and NspA, are known to bind specifically to human fH. We developed a human fH transgenic infant rat model to investigate the effect of human fH on meningococcal bacteremia. At 18 h after intraperitoneal challenge with 560 CFU of group B strain H44/76, all 19 human fH-positive rats had positive blood cultures compared to 0 of 7 human fHnegative control littermates (P < 0.0001). Human fH-positive infant rats also developed bacteremia after challenge with isogenic mutants of H44/76 in which genes encoding fHbp and NspA (⌬fHbp ⌬NspA mutant) or the lipooligosaccharide sialyltransferase (⌬lst mutant) had been inactivated. A fully encapsulated ⌬fHbp ⌬NspA ⌬lst mutant unable to sialylate lipooligosaccharide or bind human fH via the known fH ligands did not cause bacteremia, which argued against global susceptibility to bacteremia resulting from random integration of the transgene into the rat genome. In vitro, the wild-type and ⌬fHbp ⌬NspA mutant strains were killed by as little as 20% wild-type infant rat serum. The addition of 3 g of human fH/ml permitted survival of the wildtype strain in up to 60% infant rat serum, whereas >33 g of human fH/ml was required to rescue the ⌬fHbp ⌬NspA mutant. The ability of meningococci lacking expression of fHbp and NspA to cause invasive disease in human fH transgenic rats and to survive in wild-type infant rat serum supplemented with human fH indicates an additional human fH-dependent mechanism of evasion of innate immunity.

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“…These results suggest that analogous to the findings with C3 allotypes, screening for MCP, fH, and fI polymorphisms could ultimately direct management and improve patient outcome. Moreover, combined liver-kidney transplantation in appropriate cases offers a means to replace the defective fH, which is mainly produced by hepatic synthesis [37,38]. This has been the subject of recent review [39].…”

Section: Genetic Polymorphisms In Complement Proteins/regulators and mentioning

confidence: 99%

Graft-derived complement as a mediator of transplant injury

Zhou

Medof

Heeger³

et al. 2007

Current Opinion in Immunology

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Analysis of complement factor H mRNA expression: dexamethasone and IFN-.gamma. increase the level of H in L cells

Cited by 28 publications

References 36 publications

Constitutive Expression and Regulation of Rat Complement Factor H in Primary Cultures of Hepatocytes, Kupffer Cells, and Two Hepatoma Cell Lines

Constitutive Expression and Regulation of Rat Complement Factor H in Primary Cultures of Hepatocytes, Kupffer Cells, and Two Hepatoma Cell Lines

Enhanced Bacteremia in Human Factor H Transgenic Rats Infected by Neisseria meningitidis

Graft-derived complement as a mediator of transplant injury

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