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Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 73 records · Page 4Linked to original sources
PubMed1985

Role of cyclic AMP in the induction of histamine secretion from mast cells.

Immunological activation of rat peritoneal mast cells induced a transient elevation in the intracellular concentration of cyclic AMP. Enhancement or suppression of this rise by appropriate adenosine analogues produced parallel changes in histamine secretion. However, pharmacological activation of the cell with a number of diverse ligands induced histamine release without any accompanying changes in cyclic AMP. Moreover, this release was modulated by adenosine analogues in identical fashion to IGE-directed ligands but again without affecting cyclic AMP. On the basis of these results, the possible role of cyclic AMP in the induction of histamine secretion is critically considered.

Adenosine↗
PubMed1985

Isolation and properties of cardiac and other mast cells from the rat and guinea-pig.

A method is described for the enzymic dispersion into their component cells of cardiac tissues from the rat and guinea-pig. The resulting suspensions contain ca. 1% free mast cells and exhibit a low spontaneous release of histamine. The reactivity of these cells towards a number of defined chemical histamine liberators is compared with that of other connective tissue mast cells from the same animals. The results obtained are discussed in terms of the general functional heterogeneity of mast cells from different locations.

Animals↗
PubMed1985

Dual effect of antihistamines on rat peritoneal mast cells: induction and inhibition of histamine release.

A variety of H1- and H2-receptor agonists and antagonists are shown to have a dual effect on isolated rat peritoneal mast cells. At high concentrations the drugs induce histamine release while at low concentrations they inhibit the secretion of the amine evoked by antigen. These effects do not appear to be directly related. The ability of the H1-antagonists to inhibit histamine release does not appear to correlate in simple fashion with their recorded pA2 values as measured on the guinea pig ileum, suggesting that the effect is not mediated through H1-receptors. These results are discussed in terms of the clinical utility of antihistaminic drugs.

Anaphylaxis↗
PubMed1985

Effect of calmodulin inhibitors on histamine secretion from mast cells.

Histamine secretion from isolated peritoneal mast cells was inhibited by a number of calmodulin antagonists. The characteristics of the inhibition were consistent with an action after calcium influx. The rank order of potency of the compounds correlated approximately with their reported anti-calmodulin activity. These data provide tentative support for the involvement of calmodulin in stimulus-secretion coupling in the mast cell.

Animals↗
PubMed1985

Human mast cells recovered by bronchoalveolar lavage: their morphology, histamine release and the effects of sodium cromoglycate.

Mast cells make up between 0.5 and 3% (mean 1.35%) of total cells recovered by bronchoalveolar lavage (BAL). The majority of these cells have the morphological characteristics of mucosal mast cells in that they fail to stain in the alcian blue-safranin reaction after fixation in formol-saline but stain well after fixation in Carnoy's solution. Cells staining with berberine sulphate were seen in only four of the 26 lavages. BAL cells released histamine in response to anti-human immunoglobulin E (IgE) in a dose-dependent manner that was optimal at a dilution of anti-IgE of 1:100. Maximum release was obtained by 2 min. Histamine release was completely inhibited by a combination of 2-deoxyglucose (5 mmol/l) and antimycin A (1 mumol/l). Disodium cromoglycate (DSCG) significantly inhibited this histamine release at 1 mmol/l (P less than 0.02), 100 mumol/l (P less than 0.002) and 10 mumol/l (P less than 0.003), with maximum inhibition of 50.1% at 10 mumol/l.

Adult↗
PubMed1985

Studies on histamine secretion from enzymically dispersed cutaneous mast cells of the rat.

A method has been developed for the enzymic dissociation of rat skin into its component cells. The resulting suspensions contained 3-5% mast cells. The latter were intact as judged by light microscopy and exhibited a low spontaneous release of histamine. Cells obtained from actively sensitized animals released histamine on challenge with specific antigen. The process was rapid, being essentially complete within 1 min, and was both calcium-and temperature-dependent. The cells also responded to antirat IgE and to calcium ionophores but showed a selective, time-dependent reactivity toward defined chemical histamine liberators. On the basis of these results the properties of the cutaneous mast cell are compared with those previously reported for mastocytes from other sources and discussed in terms of the general heterogeneity of this cell population.

Animals↗
PubMed1985

The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response.

The ability of thapsigargin and thapsigargicin to activate mast cells and leukocytes has been investigated. The thapsigargin-induced histamine release from rat peritoneal mast cells was found to be dependent on the concentration of thapsigargin, the purity of the mast cell preparations, and the number of mast cells in suspension. Thapsigargin induced histamine release from human basophil leukocytes. Thapsigargin induced beta-glucuronidase and lysozyme release from human neutrophil leukocytes. Thapsigargin caused a release of histamine from mesentery, lung, and heart mast cells of the rat, but only to a minor extent from the corresponding guinea-pig cells. Thapsigargicin induced histamine release from mesentery, lung, and heart mast cells of the rat at concentrations from 0.1 microM but provoked only a release from the corresponding guinea-pig cells in the concentration-range 0.16 to 1.6 microM. Thapsigargin increased the cytoplasmic free calcium level in intact human blood platelets at concentrations from 3.0 nM.

Adult↗
PubMed1985

Immediate hypersensitivity reactions in epithelia from rats infected with Nippostrongylus brasiliensis.

Colonic epithelia from rats infected with the nematode Nippostrongylus brasiliensis have been studied under short circuit conditions and in response to challenge with worm antigen. Challenge from the serosal but not the mucosal side with antigen caused a transient increase in inwardly directed short circuit current. No effects were observed in comparable tissues from noninfected animals. Simultaneous measurements of short circuit current and of the fluxes of sodium or chloride ions showed there was an increase in electrogenic chloride secretion and an inhibition of electroneutral sodium chloride absorption, associated with antigen challenge. This result, together with the inhibitory effects of piretanide on the response to antigen challenge, indicate that chloride ions are a major carrier of the short circuit current response. However, the equivalence of the biophysical response to ion fluxes was not established, there being an excess of chloride secretion. The mast cell stabilizing agent, FPL 52694, significantly inhibited the current responses to antigen, while cromoglycate and doxantrazole were ineffective. Mepyramine, an H1-receptor antagonist, and indomethacin, an inhibitor of fatty acid cyclo-oxygenase, were without effect on the responses to antigen challenge. Anti-rat IgE produced qualitatively similar responses to antigen in both normal and sensitized colonic epithelia. However, the responses were significantly greater in tissues derived from infected animals. Maximally effective antigen concentrations prevented subsequent responses to anti-rat IgE in sensitized tissues, while anti-rat IgE only attenuated the responses to antigen. The ways in which antigen challenge modifies epithelial function is discussed, particularly in relation to its possible role in promoting rejection of the nematodes during secondary infection.

Animals↗
PubMed1984

The purification and characterisation of hyaluronidase from the venom of the honey bee, Apis mellifera.

Hyaluronidase has been purified from the venom of the honey bee, Apis mellifera. The purification proved remarkably difficult, requiring a large number of chromatographic steps culminating in the removal of traces of phospholipase A2 with an affinity purified rabbit anti-phospholipase A2 immunosorbent column. The purified enzyme showed a 1143-fold increase in specific activity and was homogeneous. Electrophoresis in polyacrylamide gels (12%) containing sodium dodecyl sulphate (pH 8.9) or urea (pH 2.8) and electrofocusing in polyacrylamide (5%) gave a single band. The final product contained less than 0.1% phospholipase A2 and less than 1.5% acid phosphatase and gave a single line of precipitation against rabbit anti-hyaluronidase but was not precipitated by rabbit anti-phospholipase A2. Previous reports of instability were not confirmed, and we found the enzyme to be highly stable over a wide range of temperature and pH, and to denaturing agents. Purified hyaluronidase was found to be 'sticky' when highly pure and at low concentration, and adhered strongly to Sephadex G-75. The relative molecular mass was estimated at 35 000-37 000 by gel filtration, and at 41 000 by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. A value of 50 000 was obtained by ultracentrifugation assuming a partial specific volume of 0.73 cm3/g. Hyaluronidase was found to be a minor allergen in bee venom allergic patients.

Amino Acids↗
PubMed1984

Effect of cyclic AMP, disodium cromoglycate and other anti-allergic drugs on histamine secretion from rat mast cells stimulated with the calcium ionophore ionomycin.

Cyclic AMP analogues and the anti-allergic drugs disodium cromoglycate, quercetin, doxantrazole and theophylline inhibited histamine secretion from rat peritoneal mast cells stimulated with the calcium ionophore ionomycin. The potency of the compounds varied inversely with the concentration of ionophore and with the period of incubation. The drugs were active in both the presence and absence of extracellular calcium. These results cannot be explained in terms of the postulated effect of the compounds on the receptor-mediated activation of calcium-channels. Alternative mechanisms for their action are thus considered.

Animals↗
PubMed1984

Some studies on the release of histamine from mast cells treated with polymyxin.

Polymyxin B produced a dose-dependent release of histamine from rat peritoneal mast cells. The response was non-cytotoxic and extremely rapid. The release was maximal in the presence of extracellular calcium ions but a substantial component persisted in the absence of the cation. This component was virtually abolished by pretreatment with the ionophore A23187 in the presence of a chelating agent and thus probably reflected the mobilization of intracellular stores of calcium. Hamster peritoneal cells also responded to polymyxin but were less reactive than those of the rat. Mouse peritoneal cells and guinea-pig lung mast cells responded only at very high concentrations. These results further emphasize the functional heterogeneity of mast cells from different sources. Histamine release from rat peritoneal mast cells was inhibited in dose-dependent fashion by cAMP analogues and anti-allergic drugs. The inhibitory effect varied inversely with the magnitude of the control secretion. With the exception of disodium cromoglycate, the test drugs were essentially equiactive in the presence and absence of extracellular calcium. These results are discussed in terms of the possible mode of action of these compounds.

Animals↗
PubMed1984

Calcium efflux and histamine secretion from rat peritoneal mast cells.

Purified rat peritoneal mast cells rapidly accumulated 45calcium from the external medium. The uptake was essentially unaffected by lanthanide ions but was almost totally prevented by metabolic inhibitors. Cells preloaded with 45calcium showed a steady efflux of the cation on transfer to a medium lacking the isotope. The efflux was unaffected by metabolic inhibitors but was totally dependent on extracellular sodium ions. These results indicate the operation of a sodium-calcium exchange mechanism for the extrusion of the divalent cation. Antigenic or pharmacologic stimulation of the mast cell led to a temporary suppression of calcium efflux during the period in which histamine release occurred. This effect was potentiated by phosphatidylserine and high concentrations of the lipid inhibited basal efflux. These results suggest that activation of the mast cell leads to an inhibition of calcium extrusion, thereby potentiating the induced rise in the intracellular concentration of the cation and thus augmenting the secretory response.

Animals↗
PubMed1984

Differential effects of anti-allergic compounds on peritoneal mast cells of the rat, mouse and hamster.

The effects of various inhibitors and anti-allergic drugs on histamine secretion from peritoneal mast cells of the rat, mouse and hamster have been compared. Phosphodiesterase inhibitors, cAMP analogues and beta-adrenoceptor agonists variously blocked release of the amine from all three cell types. The mouse cells were rather less sensitive to the former agents than those of the rat and hamster. Disodium cromoglycate inhibited histamine secretion from rat peritoneal mast cells, was less active against the hamster cells and completely ineffective against those of the mouse. Other chromones showed varied patterns of differential reactivity but phloretin and the flavonoid quercetin were essentially equiactive against all three cell types. The tetrazoles AH 9679 and doxantrazole prevented histamine release in each case but were significantly less active against the mouse cells. These results further emphasize the functional heterogeneity of mast cells from different sources.

Animals↗
PubMed1984

Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells.

Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin , apigenin , chrysin , and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.

Animals↗
PubMed1984

A comparison of histamine secretion from peritoneal mast cells of the rat and hamster.

Functional mast cells have been obtained by peritoneal lavage of the rat and hamster. Both cell types released histamine on stimulation with appropriate dilutions of anti-rat IgE and anti-hamster serum. The maximum response evoked by each reagent was significantly greater for the hamster cells. The release was non-cytotoxic and was in each case blocked by the corresponding soluble antigen. The rat and hamster cells responded to concanavalin A and the lectin from lentil. Phosphatidylserine (PS) potentiated the release only from the rat cells. In the absence of the lipid, the hamster cells were more reactive. The lectin from wheat germ, in the presence of PS, evoked histamine secretion only from the rat cells. Both populations were refractory to the lectin from soybean and to protein A. Rat peritoneal cells were more responsive to the basic secretagogues compound 48/80 and peptide 401 (the MCD-peptide from bee venom). These differences were less marked in the case of polylysine and polyarginine. The two cell populations responded to the calcium ionophores A23187, ionomycin and chlortetracycline. The hamster cells were significantly more sensitive to the former two liberators but markedly less reactive to chlortetracycline. Adenosine 5'-triphosphate (ATP) and dextran were potent histamine liberators from the rat cells but were totally ineffective against the hamster. Acetylcholine and carbamylcholine had no effect on either cell type. These results are discussed in terms of the functional heterogeneity of mast cells from different sources.

Animals↗
PubMed1983

Use of chlortetracycline to monitor calcium mobilization during histamine secretion from the mast cell: a cautionary note.

Purified rat peritoneal mast cells incubated with chlortetracycline showed a fluorescence emission spectrum characteristic of the membrane-bound complex with calcium ions. Treatment of the cells with chelating agents, which are thought to deplete the mast cell of sequestered calcium, led to a marked reduction in fluorescence. Activation of the cells with a number of secretagogues produced an abrupt fall in fluorescence emission, indicative of the release of bound calcium, and an accompanying liberation of histamine. These changes were, however, blocked by metabolic inhibitors and anti-anaphylactic agents, suggesting that they occurred subsequently to the exocytotic process. The significance of these findings in the application of the method to other systems is discussed.

Animals↗