Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 55 records · Page 3Linked to original sources

PubMed1987

On the mechanism of dextran-induced histamine secretion from rat peritoneal mast cells.

The mechanism of histamine release induced from isolated rat peritoneal mast cells by clinical dextran was examined in detail. The putative involvement of cell-fixed IgE antibodies in the process was discounted by a number of experimental approaches. Instead, the characteristics of the release were found to be consistent with the interaction of the polysaccharide with specific glucoreceptors on the mast cell membrane.

Animals↗

PubMed1987

Some further properties of human pulmonary mast cells recovered by bronchoalveolar lavage and enzymic dispersion of lung tissue.

The properties of human pulmonary mast cells obtained by bronchoalveolar lavage (BAL) and enzymic dispersion of lung tissue have been compared with those of basophil leucocytes. On challenge with anti-human IgE, the pulmonary cells released both histamine and the newly generated mediators prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). In contrast, the blood leucocytes released histamine but very little leukotriene and no prostanoid. Interestingly, both basophil leucocytes and BAL cells released histamine spontaneously in a hyperosmolar environment whereas dispersed lung (DL) cells showed limited reactivity under these conditions. The possible clinical significance of these findings in human bronchial asthma is discussed.

Adult↗

PubMed1987

Basophil histamine release. A study in allergy to suxamethonium.

A patient who suffered a severe hypotensive episode after induction of anaesthesia, was subsequently found to show positive skin-test responses to suxamethonium. Investigation revealed that suxamethonium induced basophils from the patient to release histamine to an extent comparable to that found after exposure to anit-IgE. Basophils from control subjects showed no such response. Basophil histamine release may offer a useful approach to the investigation of adverse drug reactions.

Adult↗

PubMed1987

Some studies on human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymic dissociation of whole lung tissue.

Human pulmonary mast cells were obtained by bronchoalveolar lavage (BAL) and by enzymic dissociation of whole lung. The cells released histamine on immunological stimulation or on exposure to a hyperosmolar environment. Cell suspensions similarly released newly generated products of arachidonic acid metabolism. Increased numbers of mast cells were recovered by BAL of asthmatic subjects and patients suffering from sarcoidosis and these cells were hyperresponsive to immunological challenge. Mast cells recovered by BAL and enzymic dissociation were differentially inhibited by antiasthmatic drugs. These data emphasize the potential role of BAL mast cells in pulmonary diseases of diverse origin.

Adolescent↗

PubMed1986

The effect of adenosine and its analogues on cyclic AMP changes and histamine secretion from rat peritoneal mast cells stimulated by various ligands.

In keeping with previous reports, immunological activation of purified rat peritoneal mast cells induced a transient elevation in the intracellular concentration of cyclic AMP which preceded or accompanied the release of histamine. Enhancement or suppression of this rise by appropriate adenosine analogues produced parallel changes in histamine secretion. However, the purinoceptor antagonist theophylline prevented the augmented rise in cyclic AMP induced by adenosine analogues but did not affect the enhancement of histamine release. In addition, pharmacological activation of the cell with a number of diverse ligands induced histamine release without any accompanying changes in cyclic AMP. This release was modulated by adenosine analogues in identical fashion to IgE-directed ligands but again without affecting cyclic AMP levels. These data clearly show that adenosine can augment histamine release independently of adenylate cyclase and seriously question the significance of the early rise in cyclic AMP as a causal event in immunological secretion of the amine.

Adenosine↗

PubMed1986

Some studies on the release of histamine from mast cells treated with d-tubocurarine.

d-Tubocurarine (dTc) released histamine in non-cytotoxic fashion from peritoneal mast cells of the rat, mouse and hamster. The response was similar to that evoked by other cationic liberators such as compound 48/80 and polylysine in that it was extremely rapid and enhanced by calcium-deprivation at suboptimal concentrations of secretagogue. Tissue mast cells obtained by enzymic dissociation of the heart, lung and mesentery of the rat and guinea pig were unreactive or hyporesponsive to the effect of dTc. The compound liberated only very small amounts of histamine from isolated preparations of perfused guinea pig heart but significantly increased the rate and contractility of the heart. These results are discussed in terms of the general functional heterogeneity of mast cells from different locations.

Animals↗

PubMed1986

Effects of antihistamines on isolated mast cells from the rat, guinea pig and man.

The effects of a range of antihistamines and related compounds on mast cells from a number of different locations have been investigated. The drugs had a dual action on all the cell types examined: at high concentrations they induced histamine release while at low concentrations they inhibited the secretion of the amine evoked by antigen. The relative potencies of the various compounds in both evoking and preventing histamine release varied from one mast cell to another. In total, these studies then further emphasise the functional heterogeneity of mast cells from different locations.

Anaphylaxis↗

PubMed1986

Some properties of mast cells obtained by human bronchoalveolar lavage.

The properties of human pulmonary mast cells obtained by enzymic dispersion of whole lung and by bronchoalveolar lavage (BAL) have been compared with those of the basophil leucocyte. The latter cell types responded with release of histamine to challenge with anti-human IgE but the dispersed cells reacted only after passive sensitisation with serum from an atopic donor. Disodium cromoglycate inhibited the release of histamine from both types of pulmonary mast cell although the characteristics of the inhibition were different in the two cases. The drug was ineffective against the basophil. Increased numbers of mast cells were recovered by lavage of asthmatic subjects and these cells responded to immunological challenge with an enhanced release of histamine. The possible clinical significance of these findings in human bronchial asthma is discussed.

Adult↗

PubMed1986

Some characteristics of histamine secretion from rat peritoneal mast cells stimulated with nerve growth factor.

Nerve growth factor (NGF) isolated from mouse submandibular gland or from snake venom produced a dose-dependent release of histamine from isolated rat peritoneal mast cells. The response was almost totally dependent on the presence of extracellular calcium ions and on added phosphatidylserine or its lyso-derivative. At high concentrations, strontium ions could substitute for calcium. The process was non-cytotoxic, relatively slow, pH dependent and blocked by polyclonal antibodies to NGF. Binding of NGF to the mast cell was not dependent on added calcium. The release was unaffected by low molecular weight glucose polymers or specific quaternary ammonium salts and thus differed from that evoked by clinical dextran or polyamines. The release was not inhibited by soluble rat IgE or IgG and was unimpaired in mast cells recovered from specific pathogen free rats. As such it did not appear to be mediated through interaction with cell-fixed antibodies. The process further differed from anaphylactic histamine release in that there was no accompanying change in the intracellular level of adenosine 3',5'-cyclic monophosphate (cyclic AMP), the activated state induced by NGF was much more persistent than that evoked by antigen, and there was no cross-desensitization between the two latter stimuli. In total, these data suggest that NGF may induce secretion from rat mast cells by interaction with a specific receptor on the plasma membrane, possibly similar to that present on sensory and sympathetic neurones.

Animals↗

PubMed1986

Lamina propria mast cells in biopsies from children with Crohn's disease.

Biopsies from actively inflamed areas of terminal ileum or colon in children with Crohn's disease were examined both for lamina propria mast cell density and histamine content. These were reduced in comparison with those of normal controls. The release of histamine from biopsies of inflamed tissue did not differ greatly from that of normal tissue, either spontaneously or after receiving an antihuman IgE challenge.

Adolescent↗

PubMed1986

Bronchoalveolar mast cells in sarcoidosis: increased numbers and accentuation of mediator release.

Bronchoalveolar lavage was carried out in 36 subjects with sarcoidosis and 20 control subjects undergoing bronchoscopy for routine diagnostic purposes. The proportion of mast cells in the lavage fluid of subjects with sarcoidosis (mean (SE) 0.84% 0.09%; p less than 0.01) when compared with that of controls (mean 0.32% (0.05%); p less than 0.01). This increase was greatest in subjects with positive gallium scans but was not correlated with the percentage recovery of lymphocytes or radiographic stage. Anti-IgE induced histamine release from the bronchoalveolar cells of 15 subjects with sarcoidosis was significantly increased at all effective doses of anti-IgE. This accentuation of histamine release was significantly greater in patients with positive gallium scans and correlated directly with the percentage recovery of lymphocytes (r = 0.7, p less than 0.005). The dose-response curve of anti-IgE induced histamine release from bronchoalveolar cells of subjects with more than 20% of lymphocytes in the lavage cell population was significantly greater than the dose-response curves of subjects with fewer than 20% of lymphocytes and of controls.

Adolescent↗

PubMed1986

On the heterogeneity of mast cells.

Mast cells from different locations are shown to vary in their histochemical, ultrastructural, cytochemical and functional properties. The clinical consequences of this heterogeneity and possible reasons for its origin are discussed.

Anaphylaxis↗

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↗