Search PubMed⌕ Search

Biomedical subjects

K Whaley

Publications and source records attributed to K Whaley.

At least 109 records · Page 6Linked to original sources
PubMed1983

Control of monocyte C2 production by cyclic AMP.

We have measured the changes in C2 production and in cyclic nucleotide levels in mononuclear leucocytes cultured in the presence of agents which change intracellular cAMP. Adenylcyclase activators, cholera toxin and phosphodiesterase inhibitors increased cAMP levels and reduced C2 production. Imidazole, hydrocortisone and prostaglandin synthetase inhibitors reduced cAMP and increased C2 synthesis. The level of cAMP after 2 hr incubation showed an inverse correlation with C2 levels in the culture supernatants. When histamine, which increases cAMP and reduces C2 production, and imidazole, which reduces cAMP and increases C2 synthesis, were added together, levels of cAMP and C2 did not differ significantly from those found in control cultures. On the basis of these observations we have concluded that changes in monocyte cAMP alter the production of C2.

Adenylyl Cyclases↗
PubMed1983

Anaphylatoxins inhibit C2 production.

Anaphylatoxins C5a and C3a and their des Arg derivatives inhibited C2 production by mononuclear phagocytes. C5a and C5adesArg which were approximately equipotent (IC50 = 10(-10) mol/l) were more effective than C3a (IC50 = 5 X 10(-8) mol/l) which was approximately 10-20-fold more potent than C3adesArg IC50 = 5 X 10(-6) mol/l). Inhibition of C2 production was only reversed slightly by the addition of either indomethacin or ETYA to the cultures. Intracellular levels of cAMP, were increased by anaphylatoxins. The level of cAMP showed a good inverse correlation with C2 levels in the culture supernatants. The data suggest that the reduction in C2 production produced by anaphylatoxins may be mediated by an increase in intracellular cAMP.

Anaphylatoxins↗
PubMed1983

Serum-treated antigen-antibody complexes inhibit the production of C2 and factor B by mononuclear phagocytes.

Antigen-antibody complexes enhanced the synthesis of C2 and factor B by human monocytes and macrophages, and C2 by guinea-pig macrophages. In contrast complexes that had been treated with serum inhibited the production of these components. The inhibitory effect of serum-treated complexes was abrogated by Fab fragments of anti-C3, anti-C3c and anti-C3d. It is therefore probable that inhibition was mediated by a C3 fragment bound to the complex. The enhancing effect of untreated complexes was reversible by serum-treated complexes, and the inhibitory action of serum-treated complexes was counteracted by untreated complexes. Such a system may be important in the regulation of the synthesis of complement components in response to local requirements.

Animals↗
PubMed1983

Inhibition of complement-mediated solubilization of antigen-antibody complexes by sera from patients with rheumatoid arthritis.

Sera and synovial fluids from patients with seropositive rheumatoid arthritis inhibit the ability of normal serum to prevent immune precipitation. Sera from patients with seronegative forms of arthritis contain little inhibitory activity. Studies of the mechanism of action of the inhibitor show that it reduces C4 consumption by antigen-antibody complexes. These findings suggest that the binding of C1 to complexes or activation of C1 is impaired. The possibility that the inhibitory activity may be mediated by rheumatoid factor is discussed. As inhibitory activity is more prevalent and of a higher level in patients with extra-articular features, it is possible that it may play a pathogenetic role.

Antigen-Antibody Complex↗
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

Endotoxaemia and complement activation in acute pancreatitis in man.

Twenty-four patients who experienced 26 attacks of acute pancreatitis were studied. Endotoxaemia, as measured by the limulus lysate assay, was present in 13 of the attacks. Six out of seven patients with systemic complications of the disease had endotoxaemia. C3 catabolism was increased in all 26 attacks of pancreatitis, and a falling level of C3 during attacks of severe pancreatitis was associated with a fatal outcome. There was statistical evidence of more complement activation in serum samples taken when patients had positive limulus lysate tests than when endotoxin was not detected in their blood.

Acute Disease↗
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↗
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↗
PubMed1982

Modulation of C2 biosynthesis by antigen-antibody complexes.

Antigen-antibody complexes prepared with BSA and immunoadsorbent purified anti-BSA enhance C2 production by human monocytes in culture. The ratio of antigen to antibody was found to influence the degree of enhancement of C2 synthesis. Complexes prepared with F(ab)2 had no effect on C2 synthesis, suggesting that the effect was mediated via the Fc receptor. Enhanced C2 production by antigen-antibody complexes was reversibly inhibited by cycloheximide (2.5 micrograms/ml). In contrast to complexes heat-aggregated rabbit IgG inhibited C2 production. The biological relevance of these findings is discussed.

Animals↗
PubMed1982

Complement activation in chronic liver disease.

Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease.

Complement Activation↗
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

Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes.

Short-term cultures of human peripheral blood monocytes were shown to synthesize the alternative pathway complement components C3, factors B (B) and D (D), and properdin, the regulatory proteins C3b inactivator (C3bINA) and beta 1H, in addition to C2, C4, and C5. B, D, properdin, C3bINA, and C2 were detected by functional assays, whereas beta 1H, C4, C3, and C5 could only be detected using immunochemical procedures. Immunoperoxidase localization studies showed that all the cells in each culture contained each component, so it is possible that all monocytes synthesize each component. It is concluded that cells of the monocyte-macrophage series form a mobile source of complement components and regulatory proteins which can be concentrated at sites of inflammation.

Cells, Cultured↗
PubMed1980

Immune complexes in Sjögren's syndrome.

Sera from 48 patients with Sjögren's syndrome were examined for immune complexes by the Raji cell assay. There was no correlation between levels of immune complexes and the degree of lymphocytic infiltration of the labial salivary glands. Serum complement levels were normal. Five patients were serially followed during the development of pseudolymphoma or malignant lymphoma. Immune complex levels in 4 of the 5 patients were generally unchanged throughout the illness and did not parallel disease activity, rheumatoid factor, or SS-A and SS-B concentrations. Possible roles for immune complexes in Sjögren's syndrome are discussed.

Antibody Formation↗
PubMed1980

Control of complement activation in membranous and membranoproliferative glomerulonephritis.

Renal biopsy specimens from 22 membranous (MGN) and 19 membranoproliferative glomerulonephritis (MPGN) patients were examined for the presence of the three regulators of the complement system; C1- inhibitor (C1--INH), C3b inactivator (C3b-INA), and beta 1H. The serum concentrations of these proteins, at the time of biopsy, were also measured. To study the modulation of complement activation by these three control proteins in MGN and MPGN, we examined the relationship between each control protein and the protein whose activity it regulates, in four ways; (a) the concordance between the presence of the control proteins and the components regulated was studied, (b) the correlations in intensity of deposition of the control and complement proteins were measured, (c) the patterns of distribution of the proteins within the glomeruli were compared, and (d) the serum levels of control proteins and components, regulated were examined. C1--INH (23 of 35 biopsies) and beta 1H (34 of 36 biopsies) were frequently deposited in both disease groups. C3b-INA was found only rarely in MPGN (4 of 19 biopsies). This is probably because the former two proteins modulate complement activation stoichiometrically, whereas C3b-INA acts enzymatically. A relationship was demonstrated between C1--INH and C1s and between beta 1H and C3 in both groups, but no such relationship was found between C3bINA and C3. Conclusion. There is no generalized deficiency in modulation of complement activation in MGN or MPGN.

Complement C1 Inactivator Proteins↗
PubMed1980

Hereditary angio-oedema: its pathogenesis and management.

Hereditary angio-oedema is a genetically-determined disease. Usually the disease is due to a deficiency of C1-inhibitor or less commonly to the production of a functionally inactive molecule. The pathogenesis and clinical features of the disease are reviewed, and discussed in relation to the homeostatic role of C1 inhibitor. Finally the therapeutic approach to the disease is described and the scientific bases for the newer therapeutic discussed.

Anabolic Agents↗