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D Lappin

Publications and source records attributed to D Lappin.

28 records · Page 2Linked to original sources
PubMed1983

A comparison of the effects of heat-aggregated and chemically cross-linked IgG on monocyte C2 production.

Heat or alkali-aggregated IgG was found to inhibit C2 production by monocytes, whereas chemically cross-linked IgG and antigen-antibody complexes stimulated C2 synthesis. Chemically cross-linked IgG was shown to inhibit monocyte EA-rosette formation presumably because it blocked monocyte Fc receptors. Furthermore stimulation of C2 synthesis was limited to polymers of the IgG1 and IgG3 subclasses. In contrast, heat-aggregated IgG failed to inhibit monocyte EA-rosette formation significantly, and all the heat-aggregated IgG subclasses inhibited C2 production. It therefore appears that physically aggregated IgG does not bind effectively to Fc receptors. As the effects of physically aggregated IgG C2 production are similar to those of the hydrophobic proteins casein and alkali-denatured human serum albumin (HSA), it is suggested that hydrophobic residues in the aggregates bind preferentially to the lipid component of the cell membrane.

Animals↗
PubMed1982

Cyclic AMP mediated modulation of complement protein production.

We have investigated the mechanisms by which cAMP analogues and phosphodiesterase inhibitors, reduced the production of C2 by monocytes in culture. Pulse label studies with 3H-labelled aminoacids showed that dibutyryl cAMP (dbcAMP) impaired the secretion of newly synthesised protein, both total (acid-precipitable) and individual complement proteins (precipitated antibody by antisera to C4, C2, C3, C5, B, P, C3b inactivator and beta 1H). The intracellular degradation of newly synthesised protein was increased in dbcAMP-treated cultures and protein synthesis was reduced. Studies aimed at defining the temporal relationships between these changes showed that protein secretion was impaired on the first day of culture, and increased degradation of newly synthesised protein was obvious by day 2. Protein synthesis was not significantly reduced until day 3 of culture. It is proposed that changes in intracellular cAMP levels may act as a second signal in the control of protein production by monocytes.

Bucladesine↗
PubMed1982

Adrenergic receptors on monocytes modulate complement component synthesis.

The addition of adrenaline, noradrenaline or phenylephrine, but not isoprenaline to monocyte cultures enhanced synthesis of the second complement component (C2). This effect was abrogated by the concomitant addition of the receptor antagonist, phentolamine, but not the beta receptor antagonist propranolol. Thus the receptor involved is an alpha adrenergic receptor. Further studies showed that the receptor was of the alpha 1 subclass as prazosin inhibited the action of adrenergic agonists. Pulse label studies using 3H-amino acids showed that the enhancement of synthesis of eight complement components (C2, C3, C4, C5, factor B, properdin, beta 1H and C3b inactivator) and total protein synthesis were also increased. The possible mechanisms underlying these changes are discussed.

Adrenergic alpha-Agonists↗
PubMed1981

Cyclic AMP-mediated modulation of the production of the second component of human complement by monocytes.

The production of the second complement component (C2) by human monocytes in culture was inhibited by increasing their intracellular concentrations of cAMP following the addition to the culture medium of dibutyryl-cyclic AMP, 8-bromo-cyclic AMP, theophylline, isobutylmethylxanthine, cholera toxin or adenosine. The effects were not due to cytotoxicity or loss of cells from the monolayers, and therefore must reflect a decreased synthesis of section of C2. Although dibutyryl-cyclic GMP enhanced C2 production, 8-bromo-cyclic GMP, ascorbic acid and sodium nitroprusside did not have this effect. These observations suggest that the action of dibutyryl-cyclic GMP is not due to elevation of cyclic GMP levels and that cyclic GMP levels do not play a major role in C2 production by monocytes.

Bucladesine↗
PubMed1981

Enhancement of monocyte complement component synthesis by antigen--antibody complexes.

Antigen--antibody complexes were found to enhance the synthesis of the complement components C2, C4, C3, C5, factor B, properdin, C3b inactivator and beta 1H by human monocytes in tissue culture. The synthesis of all components was increased by complexes in a dose-dependent fashion. Insoluble complexes formed at equivalence (antigen--antibody ratio 2:1) were more effective than complexes formed at eight times antigen excess (antigen--antibody ratio 16:1), two times antigen excess (antigen--antibody ratio 4:1) or four times antibody excess (antigen--antibody ratio 1:2). The latter three species of complexes each consist of a mixture of soluble and insoluble complexes. It was shown that total complexes (soluble and insoluble) were more potent than soluble complexes at stimulating complement component synthesis. Soluble complexes of different molecular sizes were prepared by gel-filtration chromatography; larger complexes enhance C2 synthesis to a greater extent than small complexes. The enhanced synthesis of the functionally active complement components by mononuclear phagocytes induced by antigen--antibody complexes probably facilitates the handling of complexes by promoting their solubilization and degradation.

Antigen-Antibody Complex↗
PubMed1980

Effects of histamine on monocyte complement production. I. Inhibition of C2 production mediated by its action on H2 receptors.

Histamine produced dose-dependent inhibition of the production of the second complement component (C2) by monocytes in tissue culture. The effect was not associated with either cell death, as ascertained by trypan blue exclusion, or loss of cells from the monolayer, as determined by measuring their DNA content. The specificity of the response was shown by the failure of histidine or histamine metabolites to inhibit C2 production. Preincubation of histamine with histaminase also abrogated the histamine effect. The kinetics of the effect were extremely rapid and irreversible, most of the reduction being achieved during a 5-min exposure to histamine. The H2 receptor antagonist cimetidine was able to prevent the histamine response, whereas chlorpheniramine, the H1 receptor antagonist, had no effect. Dimaprit and 4-methyl histamine, H2 receptor agonists, simulated the effect of histamine whereas the H1 receptor agonist 2-(2-aminoethylthiazole) was ineffective, confirming that the effect of histamine on C2 production by monocytes is mediated by the H2 receptors. Thus histamine, released from basophils or mast cells by the C3 and C5 cleavage products C3a and C5a respectively, may exert a negative feedback on further C3 and C5 cleavage by limiting the formation of the C3 (C42) and C5 (C423b) convertases.

Cells, Cultured↗
PubMed1980

Effect of histamine on monocyte complement production. II. Modulation of protein secretion, degradation and synthesis.

Using immunofluorescence and pulse-label studies with 3H-labelled amino acids, histamine was shown to inhibit the secretion of newly synthesized C2, C4, C3, factor B and beta 1H globulin by monocytes in culture. The findings suggested that protein synthesis was decreased, and that the degradation of newly synthesized intracellular protein was increased in histamine-treated monocytes. The observations that all monocytes in cultures containing histamine stained for C2, C4, and C3, factor B and beta 1H, when secretion was impaired, shows that all monocytes synthesize these proteins. These results demonstrate a negative feedback loop on C3 and C5 cleavage. The anaphylotoxins, C3a and C5a, formed as a result of C3 and C5 cleavage, release histamine from mast cells and basophils. Histamine, by inhibiting the production of C4, C2, and C3 and factor B by mononuclear phagocytes, inhibits further C3 and C5 cleavage by restricting the formation of C42, C423b and C3bBbP.

Amino Acids↗