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Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 19 recordsLinked to original sources
PubMed1992

Mast cell heterogeneity: evidence that mast cells isolated from various connective tissue locations in the rat display markedly graded phenotypes.

The present study has extended histochemical and functional investigations into rat mast cell heterogeneity using isolated mast cells from four connective tissue locations; the peritoneum, mesentery, lung and skin. On histological examination, mast cells from these locations displayed a range of phenotypes following formalin fixation and staining with Alcian blue/safranin O, suggesting the existence of both chondroitin sulphate and heparin proteoglycans in varying proportions in these cell types. Functional studies using the structurally diverse polycationic secretagogues, compound 48/80, the polyamino acids, polymyxin B, substance P, ACTH1-24, mastoparan, protamine sulphate, histone, d-tubocurarine and ranitidine confirmed the existence of such phenotypic gradation. This investigation highlights the inappropriate usage of the terms CTMC and MMC which represent two phenotypic extremes between which a gradation of phenotypes clearly exists.

Animals↗
PubMed1991

Mast cells from human gastric mucosa: a comparative study with lung and colonic mast cells.

Mast cells isolated from human gastric mucosa released histamine on challenge with IgE-directed ligands and calcium ionophores but were essentially unresponsive to a variety of non-immunological stimuli. Moreover, immunologically induced histamine secretion from these cells was inhibited by a number of anti-allergic agents including anti-asthmatic chromones, beta-adrenoceptor agonists and phosphodiesterase inhibitors. In total, these data indicate that mast cells from the human gastric mucosa are in many respects functionally similar to their lung and colonic counterparts.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

The human skin mast cell: a comparison with the human lung cell and a novel mast cell type, the uterine mast cell.

The functional and histochemical properties of isolated mast cells from human skin, uterine myometrium and lung parenchyma were compared. The skin cell showed a marked difference in responsiveness to both secretagogues and anti-allergic compounds when compared to mast cells from the uterus and lung. The latter cell types responded more strongly to immunologically-directed ligands and calcium ionophores than the skin cell. However, the skin cell released histamine in response to a wide variety of polycationic compounds whilst the lung and uterine cells were essentially refractory to these agents. The antiallergic drugs, disodium cromoglycate (DSCG) and nedocromil sodium, were weakly inhibitory against the skin cell but were in contrast more effective against the lung and uterine cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Characteristics of histamine secretion from mast cells stimulated with sodium orthovanadate and other vanadium compounds.

Sodium orthovanadate was found to be an effective histamine liberator from serosal mast cells of the rat and mouse. The release process was slow, non-cytotoxic and strongly dependent on pH and extracellular calcium. The effect was highly tissue and species specific and human basophil leucocytes, human lung mast cells and tissue mast cells of the rat and guinea pig were only weakly responsive or essentially unreactive. Other oxyanions of vanadium with the metal in the (+V) oxidation state also evoked histamine release from rat peritoneal mast cells but neither vanadyl sulphate (+IV oxidation state) nor the analogous orthophosphate anion were effective secretagogues. On the basis of these results, the possible mechanism of action of vanadate is discussed.

Animals↗
PubMed1990

Effects of antihistamines on isolated rat peritoneal mast cells and on model membrane systems.

We have examined the effect of a range of histamine H1- and H2-receptor agonists and antagonists on rat peritoneal mast cells. Most of the compounds had a dual action: at low concentrations they inhibited the histamine release produced by immunologic activation of the cell whereas at higher concentrations they themselves induced a cytotoxic release of the amine. The test agents did not affect intracellular levels of cyclic AMP. In model systems, the majority of the drugs had no effect on the integrity of artificial liposomes but did protect rat erythrocytes against osmotic shock. We then propose that these agents produce their effects on mast cells by a direct action on the cell membrane, with low concentrations becoming incorporated into the bilayer in such a way as to stabilize the structure and high concentrations disrupting the membrane and leading to cell lysis.

Animals↗
PubMed1990

Histamine secretion from mast cells stimulated with ATP.

Adenosine 5'-triphosphate (ATP) induced a non-cytotoxic, calcium-dependent release of histamine and prostaglandin D2 from rat serosal mast cells. The effect was tissue and species specific. In particular, tissue mast cells from the guinea pig and man were totally unresponsive. The release evoked by the nucleotide was unaffected by antiasthmatic chromones but was inhibited by structurally related flavonoids and by cAMP-active drugs. Secretion was blocked both by the P2Y-purinoceptor antagonist reactive blue 2 and the P2X-antagonist suramin, whereas the P2-agonists 2-methylthio ATP, alpha, beta- and beta, gamma-methylene ATP were inactive. These findings indicate that ATP acts through a novel purinoceptor or binding site which is present on certain types of mast cells.

Adenosine Triphosphate↗
PubMed1990

Histamine secretion from mast cells stimulated with bradykinin.

Bradykinin and a range of peptide analogues induced a dose-dependent release of histamine from rat peritoneal mast cells. The characteristics of the release were not consistent with the involvement of defined bradykinin receptors but indicated that the peptide acted through the putative mast cell polyamine receptor. Consistently, the effect of bradykinin was largely confined to serosal mast cells of the rat and hamster, while human histaminocytes were essentially unresponsive. These data do then not support a general role for kinin-induced activation of mast cells in human allergic disease.

Animals↗
PubMed1990

Mast cells from human colonic mucosa and submucosa/muscle: a comparison with human lung mast cells.

The functional properties of enzymically dispersed mast cells from human lung parenchyma, colonic mucosa and colonic submucosa/muscle were compared. In general, the cells responded in a similar fashion to the histamine releasing action of a variety of immunological and non-immunological stimuli. However, some differences were observed in their responses to anti-allergic compounds. In total, these data indicate that there are subtle variations between human colonic and pulmonary mast cells but that these differences are much less sharply defined than in the rodent.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Non-IgE-mediated mast cell stimulation.

The effect of a variety of non IgE-mediated stimuli on histamine release from mast cells from different locations is described. Sensory neuropeptides are shown to resemble other polycationic compounds in preferentially activating mast cells from the rat while having a limited effect on human mast cells, except possibly those from skin. Similar results were obtained with the putative non-adrenergic, non-cholinergic neurotransmitter ATP, thereby questioning the role of neuronal mast cell activation in allergy and inflammation. Bradykinin also acted selectively against rat cells while complement-derived and formylmethionyl peptides were effective against human basophils and cutaneous mast cells. The latter results may indicate a role for the skin cell in local inflammatory responses involving complement activation and in host resistance to bacterial infection. Rat mast cells and human basophils were most responsive to hyperosmolar challenge but significant effects were obtained from human pulmonary mast cells obtained by bronchoalveolar lavage. The latter cells may thus be implicated in exercise-induced asthma. The plasma substitute dextran was a specific secretagogue for the rat while morphine sulphate largely induced histamine release from human cutaneous mast cells. The latter result may account for anaphylactoid reactions to the opiate. In total these data emphasize the functional heterogeneity of mast cells from different locations and highlight the particular pharmacological properties of the skin mast cell in man.

Animals↗
PubMed1989

Active sensitization does not increase the responsivity of rat peritoneal mast cells to diverse chemical stimuli.

Peritoneal mast cells from specific pathogen-free rats that had been sensitized to the nematode Nippostrongylus brasiliensis released histamine in a dose-dependent fashion on challenge with antigen, anti-rat IgE, anti-rat IgG and concanavalin A. Cells from non-sensitized animals showed weak or insignificant responses to these agents. However, the two preparations did not obviously differ in their reactivity to a range of pharmacological agents including ATP, dextran, polyamines and calcium ionophores. Both populations were refractory to cholinergic stimulation. These results show that active sensitization does not per se lead to a global increase in mast cell reactivity or releasability.

Adenosine Triphosphate↗
PubMed1989

Some further characteristics of histamine secretion from rat mast cells stimulated with sodium orthovanadate.

Sodium orthovanadate induced a release of histamine from rat peritoneal mast cells. Other oxyanions of vanadium with the metal in the +V oxidation state also evoked histamine release but neither vanadyl sulphate (+IV oxidation state) nor the analogous orthophosphate anion were effective secretagogues. The release evoked by vanadate was selectively inhibited by the anion channel blocker SITS, and by theophylline and Bu2cAMP, but was unaffected by disodium cromoglycate and lanthanum ions. These results are discussed in terms of the possible mode of action of vanadate.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1989

Effects of antihistamines on isolated human lung mast cells, basophil leucocytes and erythrocytes.

Low concentrations of H1- and H2-receptor directed compounds inhibited the immunologic secretion of histamine from human lung mast cells and basophil leucocytes and protected human erythrocytes from hypotonic lysis. Higher concentrations induced a release of the amine from the histaminocytes. These results are discussed in terms of the possible membrane effects of the test compounds.

Basophils↗
PubMed1989

Divalent cation dependence of the inhibition by phenothiazines of mediator release from mast cells.

1. The divalent cations calcium, strontium and barium--and in that order of decreasing effectiveness--were capable of supporting the stimulated release of histamine from rat peritoneal mast cells (RPMC). 2. The responsiveness of mast cells to stimulation in the presence of divalent cations was, in general, markedly enhanced when the cells were first depleted of their intracellular calcium stores. 3. The putative calmodulin antagonists, chlorpromazine, promethazine, thioridazine (phenothiazines) and W-7 (a naphthalene sulphonamide) all inhibited histamine release in the presence of divalent cations in both untreated cells and in RPMC depleted of their intracellular calcium. 4. Histamine release induced by antigen, compound 48/80 and ionophore A23187 was inhibited by this class of compounds most effectively in the presence of extracellular barium, less so in the presence of strontium and least so in calcium-containing media. 5. In the experimental situation where the extracellular calcium concentration was reduced (less than 1 mM), the phenothiazines inhibited the stimulated release of histamine more effectively. 6. In toto, these results suggest that strontium and barium, as well as calcium, can support histamine release from RPMC by directly interacting with an intracellular divalent cation-binding site that may be calmodulin. As a consequence, one mechanism by which the phenothiazines and W-7 may modulate the secretory response could reflect an antagonism of a divalent cation interaction at that same site, although other additional potential sites of inhibitory action are indicated, dependent on the stimulus employed for secretion.

Animals↗
PubMed1989

Characteristics of histamine secretion induced by neuropeptides: implications for the relevance of peptide-mast cell interactions in allergy and inflammation.

A variety of basic, sensory neuropeptides induced the release of histamine from rat peritoneal mast cells. However, a wide range of other polycationic agents, such as compound 48/80, the mast-cell-degranulating peptide from bee venom and polylysine also activated this cell type. Histamine release induced by all of these agents had characteristic features in common. In each case, the process was extremely rapid, essentially independent of added calcium or phospholipids, not mediated through cell-fixed antibodies, and inhibited by antagonists of the so-called polyamine receptor. The release was also very species- and tissue-specific. All of the compounds were most active against rat serosal mast cells. Tissue mast cells of this species and peritoneal mast cells of other rodents showed graded responses while guinea pig and human mast cells were unreactive. On the basis of these results, the possible role of peptide-mast cell interactions in neurogenic models of inflammation is discussed.

Animals↗
PubMed1989

Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from mast cells from various locations.

Nedocromil sodium and sodium cromoglycate inhibited histamine release from rat peritoneal mast cells. Tachyphylaxis was observed with both drugs. The 2 compounds were extremely selective in their action, being less active against peritoneal mast cells from the hamster and completely ineffective against mast cells from the mouse. Human basophil leucocytes, tissue mast cells of the guinea-pig and rat intestinal mast cells were also unresponsive. Both drugs inhibited immunological histamine release from human pulmonary mast cells obtained by bronchoalveolar lavage (BAL) and, less effectively, from lung parenchyma. Nedocromil sodium was about 1 order of magnitude more potent than sodium cromoglycate in each case. Tachyphylaxis was observed with the dispersed lung, but not with the cells obtained by BAL, and the degree of inhibition varied inversely with the magnitude of the secretory response. The possible clinical significance of these observations is discussed.

Animals↗