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Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 91 records · Page 5Linked to original sources
PubMed1986

The function and properties of human lung mast cells.

Mast cells may be recovered from human subjects by bronchoalveolar lavage. Such bronchoalveolar mast cells will release histamine in response to IgE-dependent challenge in a reaction that is dose-, time- and energy-dependent. They possess functional characteristics distinct from dispersed human lung mast cells. The percentage of mast cells within the bronchoalveolar cell population is critically dependent upon the underlying pathology. Greater numbers of mast cells may be recovered from the bronchoalveolar compartment of extrinsic asthmatics than from controls. In addition, bronchoalveolar mast cells from asthmatic subjects show an increased releasability of histamine in response to anti-IgE. Antigen challenge also leads to the release of histamine in vitro, demonstrating the potential for the antigen-specific initiation of bronchoconstriction in these subjects. Spontaneous release of histamine from bronchoalveolar mast cells of asthmatic subjects was also greater than in controls (up to 46%), a feature which may be related to non-immunological mechanisms of bronchoconstriction. Such non-immunological mechanisms have been further investigated utilising mannitol as a model of hyperosmolar histamine release. Mannitol induced a dose-dependent release of histamine from bronchoalveolar mast cells of normal subjects, and this release was significantly inhibited by sodium cromoglycate. The leukotrienes are putative major mediators of human asthma. After challenge with anti-IgE in vitro, dose-dependent release of leukotriene C4 and prostaglandin D2 occurs from the bronchoalveolar cells of normal subjects. The release of PGD2 shows significant correlation with histamine release. Lying superficially, bronchoalveolar mast cells would be readily accessible to inhaled antigen. Mediator release from such cells may be relevant to the pathogenesis of asthma.

Animals↗
PubMed1986

Comparison of the histamine-releasing action of substance P on mast cells and basophils from different species and tissues.

The action of the neuropeptide substance P as a histamine-releasing agent has been compared in histamine-containing cells from a variety of different tissues and species. Peritoneal mast cells from rat, mouse and hamster but not human cells gave a concentration-dependent release of histamine in response to substance P. Release was greater in the absence than in the presence of calcium in the extracellular medium. Mast cells from rat mesentery, lung and heart released histamine in response to substance P, but heart mast cells responded only weakly. All guinea-pig mast cells and histamine-containing cells from human tissues did not give any substantial substance-P-induced release of histamine. The data provides further evidence for the functional heterogeneity of histamine-containing cells.

Animals↗
PubMed1986

A comparison of nedocromil sodium and sodium cromoglycate on human lung mast cells obtained by bronchoalveolar lavage and by dispersion of lung fragments.

Bronchoalveolar lavage (BAL) mast cells provide a useful tool with which to screen potential therapeutic agents for human airway diseases. This study was therefore designed to compare the activity of nedocromil sodium and sodium cromoglycate in inhibiting anti-IgE induced histamine release from human mast cells obtained by BAL and from dispersed lung (DL) fragments. After 10 min pre-incubation with the mast cell preparations, both drugs displayed greater inhibition of histamine release from BAL than from DL mast cells. Under optimal conditions of 10 min pre-incubation with BAL and none with DL mast cells, nedocromil sodium showed significantly more activity than sodium cromoglycate on both BAL and DL mast cells.

Adult↗
PubMed1985

On the immunology of nerve growth factor.

We report some experiments on the immunological properties of nerve growth factor from the venom of Heloderma horridum and from bull seminal vesicles. On the basis of these results, taken together with results already in the literature, we propose an operational definition of the term nerve growth factor.

Animals↗
PubMed1985

Bronchoalveolar mast cells in extrinsic asthma: a mechanism for the initiation of antigen specific bronchoconstriction.

Bronchoalveolar lavage performed in 10 patients with extrinsic asthma and 14 controls yielded similar recoveries of fluid and cells. Mast cells and eosinophils, however, formed a greater proportion of the cells recovered from the asthmatic subjects (p less than 0.001 for mast cells; p less than 0.01 for eosinophils), the histamine content of the lavage cells being correspondingly increased (p less than 0.01). Both the percentage of mast cells and the histamine content of lavage cells were significantly inversely correlated with the forced expiratory volume in one second (FEV1; expressed as percentage of predicted) and with the ratio of FEV1 to forced vital capacity before lavage. There was also a significant inverse correlation between the concentration of histamine required to produce a 20% fall in FEV1 and the percentage of mast cells recovered (p less than 0.05). When incubated with antihuman IgE bronchoalveolar mast cells from asthmatic subjects released a significantly increased proportion of total cellular histamine than cells from control subjects at all effective doses of anti-IgE. By contrast, dose response curves for IgE dependent histamine release from peripheral blood leucocytes were similar in asthmatics and controls. Specific antigen led to release of histamine from bronchoalveolar cells and peripheral blood leucocytes of asthmatic subjects but not controls. Lying superficially within the airways, bronchoalveolar mast cells would be readily exposed to inhaled antigen and would release mediators directly on to the airway surface. Their immunological response suggests that they are likely to be important in the pathogenesis of airflow obstruction in asthma.

Adult↗
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↗