Biomedical subjects

D F Lappin

Publications and source records attributed to D F Lappin.

22 records · Page 2Linked to original sources

PubMed1990

Modulation by interferons of the expression of monocyte complement genes.

Interferons-alpha, -beta and -gamma (IFNs-alpha, -beta and -gamma) stimulated the synthesis of the second complement component (C2), Factor B (B) and C1 inhibitor (C1-inh) by human monocytes in vitro. The degree of increase of the secretion rates of C2, B and C1-inh was dose-dependent and proportional to increases in the abundances of their respective mRNAs. IFN-gamma was the most effective at stimulating monocyte C1-inh synthesis, whereas IFN-alpha and IFN-beta were marginally more effective at stimulating monocyte C2 and B synthesis. Kinetic studies showed that the effect of the IFNs was rapid, with maximum stimulation occurring within 1-2 h for all three proteins. After the removal of IFNs from cultures the C1-inh mRNA abundance remained elevated for over 24 h in IFN-gamma-treated monocytes but returned to control levels within 8 h in IFN-alpha-treated and IFN-beta-treated monocytes. The abundances of C2 mRNA and B mRNA also returned to basal values within 8 h after removal of any of the three cytokines from the cultures. Both IFN-alpha and IFN-beta acted synergistically with IFN-gamma to stimulate synthesis of C1-inh and B. This synergistic effect only occurred when the cytokines were present in the cultures simultaneously. The effects of IFN-gamma plus IFN-alpha or IFN-beta on C2 synthesis appeared to be additive rather than synergistic. IFN-gamma inhibited synthesis of C3 by monocytes, but IFN-alpha and IFN-beta had no effect on the synthesis of this protein. Furthermore, none of the three cytokines had any effect on the expression of actin mRNA in monocytes.

Cells, Cultured↗

PubMed1989

Regulation of hepatic synthesis of C3 and C4 during the acute-phase response in the rat.

Following the i.p. injection of casein, rats showed increased serum levels of C4 and C3. C4 levels peaked on day 2 and returned to normal by day 4, while C3 levels peaked on day 3 before returning to normal on day 4. These changes were paralleled by changes in the hepatocyte synthesis rates of these two proteins. Macrophages, isolated from the peritoneal cavities of rats on days 1 to 7 (day-1 to day-7 macrophages) following i.p. injection of casein, were cultured in vitro, and the peritoneal macrophage-conditioned media (PMCM) assayed for their abilities to stimulate synthesis of C4 and C3 by hepatocytes from control rats. Day-2 PMCM selectively stimulated synthesis of C4, while day-3 and day-4 PMCM selectively stimulated C3 synthesis. These activities were called C4-hepatocyte stimulating factor (C4-HSF) and C3-HSF, respectively. The addition of anti-interleukin (IL) 1, tumor necrosis factor (TNF)-alpha, TNF-beta, IL 6 or interferon (IFN)-gamma antibodies to day-2 PMCM did not affect C4-HSF activity, and none had any effect on C3-HSF activity in day-4 PMCM. However, the addition of anti-IL 1 to day-4 PMCM resulted in the re-expression of C4-HSF activity as well as loss of thymocyte proliferative activity. C4-HSF activity could also be detected in day-4 PMCM by separating it from IL 1 activity using gel filtration chromatography. Furthermore the addition of recombinant IL 1 beta to day-2 PMCM prevented the expression of C4-HSF activity. Thus IL 1 appears to play a regulatory role in the acute-phase response in the rat, by preventing the expression of C4-HSF activity. The identities of C4-HSF activity and C3-HSF are still unknown but we believe that C3-HSF activity could be IL 6 as it has a similar molecular weight (30 kDa) and purified human IL 6 was more effective than IL 1, TNF-alpha or TNF-beta in stimulating C3 synthesis by rat hepatocytes. C4-HSF activity appears to be a property of a previously undescribed cytokine. It is not IL 1 alpha or beta, TNF-alpha or -beta, IL 6 or IFN-gamma.

Acute-Phase Reaction↗

PubMed1989

Monocyte C1-inhibitor synthesis in patients with C1-inhibitor deficiency.

Monocytes of seven out of eight patients with type 1 C1-inhibitor (C1-inh) deficiency (HAE) produced 40% as much C1-inh as monocytes from normal donors (controls). In contrast, monocytes from three patients with type 2 and three patients with acquired C1-inh deficiency produced similar amounts of C1-inh as controls. Recombinant gamma-interferon (gamma-interferon 10 ng/ml) stimulated C1-inh production of C1-inh (eight-10-fold) by control and patients' monocytes. Monocytes from patients with type 1 HAE contained 40% the level of C1-inh messenger ribonucleic acid (mRNA) found in control monocytes. Gamma-interferon increased the abundance of C1-inh mRNA by the same extent in both control and patients' monocytes. C1-inh protein and mRNA were undetectable in the monocytes of one patient, unless stimulated by gamma-interferon. Under these conditions, his monocytes produced comparable amounts of C1-inh (protein and mRNA) as gamma-interferon-stimulated monocytes of the other type 1 HAE patients. The data suggest that in most type 2 HAE patients there is a lesion in the C1-inh gene such that mRNA is transcribed by a single allele.

Angioedema↗

PubMed1982

Prostaglandins and prostaglandin synthetase inhibitors regulate the synthesis of complement components by human monocytes.

The addition of prostaglandins E2 (PGE2), PGD2, PGI2, 6-keto PGF1 alpha and thromboxane B2 (TXB2) to human monocyte cultures, inhibited the production of the second component of complement (C2). PGF2 alpha did not significantly affect C2 production. As the former compounds, but not the latter increase intracellular cAMP, it was thought that the effect was mediated by this action. The addition of cyclo-oxygenase and lipoxygenase inhibitors to monocyte cultures enhanced the synthesis of complement components and other proteins in a dose-dependent fashion: cyclo-oxygenase inhibitors being more potent in this regard than lipoxygenase inhibitors. The enhancing effect of cyclo-oxygenase inhibitors paralleled their ability to inhibit cyclo-oxygenase activity. The enhancement of C2 synthesis by the addition of cyclo-oxygenase and lipoxygenase inhibitors was reversed by the addition of PGs to the cultures. It is concluded that the production of PG by monocytes could provide an endogenous mechanism to control the synthesis of complement components and other proteins.

Arachidonic Acids↗