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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

Effects of phorbol ester, serine phospholipids, and calcium on histamine release from mast cells and basophils.

The effects of calcium, serine phospholipids and the phorbol ester tetradecanoylphorbol acetate (TPA), a known activator of protein kinase C, have been examined on mastocytes from different sources. A complex and differential interaction between these agents and histamine secretion was observed in human basophil leucocytes and in peritoneal mast cells from the rat, mouse and hamster. On this basis, the possible role of kinase C in histamine release is discussed.

Animals↗

Histamine secretion from mast cells stimulated with somatostatin.

Histamine release from isolated mast cells stimulated with somatostatin resembled that induced by other basic agents. The process was rapid, independent of added calcium or phospholipids, non-cytotoxic, species and tissue specific, not mediated through cell-fixed antibodies or glucoreceptors, and inhibited by antagonists of the polyamine receptor. Somatostatin and other polycations may then act through a common receptor or binding site on the mast cell membrane.

Animals↗

Some studies on the isolation and properties of pulmonary mast cells from the pig.

Mast cells were isolated by the enzymic dissociation of lung tissue from the pig. The responses of these cells to a variety of histamine liberators and anti-allergic drugs were examined. On the basis of these findings, the possible use of porcine pulmonary mast cells in the study of immediate hypersensitivity reactions is discussed.

Animals↗

Cardiac and renal mast cells: morphology, distribution, fixation and staining properties in the guinea pig and preliminary comparison with human.

In guinea pig (GP) and human heart and kidney cell or tissue preparations fixed with Carnoy's fluid (but not with formol-saline), mast cells (MC) were extremely well preserved and could be detected after staining with alcian blue (AB). Although histamine content and distribution in GP and human heart appeared to be different, morphological and histochemical studies of MC suggested a similarity between the two species and a clear distinction from rat peritoneal MC.

Animals↗

Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from human lung mast cells.

Sodium cromoglycate and nedocromil sodium produced a dose dependent inhibition of histamine secretion from human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymatic dissociation of lung parenchyma. Both compounds were significantly more active against the lavage cells than against the dispersed lung cells, and nedocromil sodium was an order of magnitude more effective than sodium cromoglycate against both cell types. Tachyphylaxis was observed with the parenchymal cells but not with the lavage cells. Nedocromil sodium and sodium cromoglycate also inhibited histamine release from the lavage cells of patients with sarcoidosis and extrinsic asthma.

Asthma↗

Guinea pig mast cells: comparative study on morphology, fixation and staining properties.

We have studied the distribution of mast cells (MC) in different tissues of the guinea pig (GP), and certain aspects of their histochemical and cytochemical properties. In preparations fixed with Carnoy's fluid, MC were extremely well-preserved and were detected in all tissue sections and cytocentrifuge smears obtained from enzymically dispersed cells after staining with alcian blue at pH 0.5-2.2. In formol-saline-fixed preparations, there was a substantial reduction in MC counts. Most of the tissue MC were located interstitially and in the perivascular connective tissue. A small proportion of MC was located in certain organ- or tissue-specific structures. When counted manually, MC comprised 0.43-3.1% of the cell population obtained by enzymic dispersion. This proportion was higher than that obtained by the automated Technicon H6000 basophil system, but the two counting systems confirmed organ differences in MC counts. MC in different GP tissues varied in size, morphology, histamine content and degree of susceptibility to formol-saline fixation. The granules of GP connective tissue MC differed from those of rat peritoneum in failing to take the fluorescent stain berberine sulphate which has greater affinity for the highly sulphated glycosaminoglycans such as heparin, and in having some morphological and histochemical similarity to 'mucosal' MC.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗