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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is known that the release of granule-associated inflammatory amines by isolated mouse tissue-type mast cells is subject to regulation in vitro by a number of cytokines that are produced during the immune response. In this study we investigated whether mast cell secretory function might also be subject to regulation in vivo during active sensitization. Mice were sensitized with one of three chemical allergens (trimellitic anhydride, TMA; 2,4-dinitrochlorobenzene, DNCB; or oxazolone) all of which induce contact sensitization and one of which (TMA) in addition causes immediate hypersensitivity. Peritoneal mast cells isolated from treated mice and sensitized passively with IgE released a greater proportion of cellular serotonin (5-HT) on stimulation either by anti-IgE or by specific antigen than did cells isolated from vehicle-treated controls. These results show that the function of mast cells is susceptible in vivo to regulatory influences that result from induction of an immune response.
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PMID:Sensitization of mice to chemical allergens modulates the responsiveness of isolated mast cells to IgE-dependent activation. 847 34

We report that stem-cell factor (SCF), the ligand of the receptor encoded by the c-kit proto-oncogene, is a potent activator of degranulation of rat peritoneal mast cells in vitro and in vivo. Freshly isolated, purified mast cells were relatively unresponsive to SCF (4-500 ng/ml) but progressively acquired responsiveness to this agent, assessed as serotonin (5-HT) release, during 48 hr culture in vitro. The cells showed a similar kinetic pattern of acquisition of responsiveness to anti-IgE but responded fully to calcium ionophore A23187 or compound 48/80 regardless of time in culture. Acquisition of mast cell responsiveness to SCF or anti-IgE was not due to serum factors or to recovery from the Percoll purification procedure. During culture, mast cell expression of the SCF receptor (SCFR) increased, and this may explain in part the increased responsiveness to SCF. However, surface IgE expression remained constant, and the increased responses to anti-IgE therefore must reflect changes in components of the secretion-coupling pathway that are activated subsequent to IgE cross-linking. The unresponsiveness of freshly isolated peritoneal mast cells to SCF or anti-IgE does not reflect a state of in vivo unresponsiveness, as peritoneal mast cells degranulated in vivo in response to these agents. We conclude that in terms of their responsiveness to SCF or anti-IgE, cultured tissue mast cells may be more representative than freshly isolated mast cells of secretory function in vivo, and therefore may be more appropriate for physiological or pharmacological studies of SCF- or IgE-dependent secretory responses.
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PMID:Stem-cell factor, the kit ligand, induces direct degranulation of rat peritoneal mast cells in vitro and in vivo: dependence of the in vitro effect on period of culture and comparisons of stem-cell factor with other mast cell-activating agents. 855 81

Fourty antemortem and 30 postmortem gunshot wound samples of human skin were studied by immunohistochemical method. The 5-HT was seen mainly in wound edge, papillary layer, hypodermis and surrounding tissue of all antemortem gunshot wounds. The 5-HT was also discovered on the postmortem gunshot wounds which occurred within 8 minutes after death. The result showed that immunohistochemical staining of 5-HT be useful for diagnosing the antemortem gunshot wound. It also demonstrated that the mast cells of human do not contain 5-HT. We also studied the rate of mast cell degranulation of gunshot wounds of human skin by toluidine blue staining. The rate of mast cell degranulation of antemortem gunshot wounds increased (50%), and it was higher than that of postmortem gunshot wounds, suggesting that the rising of degranulation rate is a sign of antemortem injury.
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PMID:[Immunohistochemical study of 5-HT on gunshot wound of human skin]. 873 65

Previous studies of cutaneous T cell-mediated responses in mice have obtained pharmacologic, morphologic, and immunologic evidence pointing to a critical role for local mast cells in release of the vasoactive amine serotonin (5-HT) to mediate early, initiating events that are required for elicitation of these responses. However, the role of mast cells in initiating these T cell-mediated cutaneous responses has been questioned due to the presence of relatively intact delayed-type hypersensitivity responses, such as contact sensitivity (CS), in mast cell-deficient mice whose skin contains only 1 % normal mast cell numbers. The contribution of other potential local sources of 5-HT, such as circulating platelets, at the site of a delayed-type hypersensitivity or CS response in these mast cell-deficient strains, has not been investigated. Therefore, we studied the effect of systemic platelet depletion, produced with an anti-platelet Ab, on blood and tissue levels of 5-HT, and on in vivo T cell-mediated cutaneous sensitivity responses, in W/Wv and Sl/Sld mast cell-deficient mice. The results showed that: 1) platelet depletion severely reduced whole blood 5-HT; 2) tissue levels of 5-HT, in mast cell-deficient mice, depended in large part on the presence of circulating platelets, and 3) specific depletion of platelets markedly suppressed CS responses in both W/Wv and Sl/Sld mast cell-deficient mice, and only moderately reduced CS in normal +/+ congenic mast cell-sufficient controls, but did not decrease CS in beige mice, with platelet granules that are defective in storage of 5-HT. We concluded that platelets may provide 5-HT crucial for the initiation of cutaneous T cell-mediated immune responses, such as CS.
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PMID:Delayed-type hypersensitivity in mast cell-deficient mice: dependence on platelets for expression of contact sensitivity. 875 2

Stem cell factor (SCF) is potent activator of degranulation of rat peritoneal mast cells in vitro and may promote mast cell activation under certain circumstances in vivo. In this study we report that the anti-inflammatory glucocorticoid dexamethasone (DEX) and the immunosuppressive cyclosporin A (CsA) are both effective inhibitors of SCF-induced degranulation of rat peritoneal mast cells in vitro, measured as release of serotonin (5-HT). Of the two drugs, DEX was the more potent with near maximal inhibition reached at 10(-8) M, whereas a graded inhibition was seen with CsA in the range 10(-8)-10(-6) M. DEX was equally effective in inhibiting the release of 5-HT induced by either SCF or anti-IgE, but was less effective in inhibiting release induced by compound 48/80 or calcium ionophore A23187. CsA produced a similar degree of inhibition of degranulation induced by SCF, anti-IgE or ionophore, but was without effect on the response to compound 48/80. Neither DEX nor CsA had any significant effect on mast cell surface expression of the SCF receptor or IgE antibody. We conclude that both DEX and CsA inhibit components of the secretion-coupling pathways that are triggered following either SCF receptor engagement or cross-linking of IgE, but that these drug differentially influence mast cell secretion induced by compound 48/80 or the calcium ionophore A23187.
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PMID:Dexamethasone or cyclosporin A inhibits stem cell factor-dependent secretory responses of rat peritoneal mast cells in vitro. 888 Feb 26

Despite many reports that serotonin (5-HT) inhibits gastric acid output, the role and mechanism of action of endogenous 5-HT to modulate gastric secretion remain unclear. Vagal stimulation enhanced the basal rate of 5-HT release into both the gastric lumen (600%) and the portal circulation (265%) of the rat. The peak rate of 5-HT release into the portal circulation was 1,000-fold higher that luminal release (12 micrograms/min and 1.2 ng/min, respectively). To elucidate site(s) of action of 5-HT to inhibit acid secretion, several approaches were taken. Intraluminal perfusion of exogenous 5-HT to encompass enhanced levels seen after vagal stimulation did not reduce gastric acid output. In contrast, administration of systemic 5-HT, which raised portal venous 5-HT to similar levels as vagal stimulation, had a marked antisecretory effect. Chemical or surgical ablation of enteric or sympathetic nerves innervating the stomach did not attenuate the inhibitory effect of exogenous 5-HT on gastric acid output. The antisecretory effect of systemic 5-HT was insensitive to pretreatment with piroxicam, doxantrazole, close gastric intra-arterial sodium nitroprusside, somatostatin monoclonal antibody, or bilateral adrenalectomy. The results suggest that 5-HT is released from endogenous stores into the portal circulation in sufficient quantities after vagal stimulation to alter gastric physiology and that its action is independent of the autonomic nervous system, gastric mucosal prostaglandins or somatostatin, mucosal mast cell or adrenal constituents, or changes in gastric mucosal blood flow.
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PMID:Gastric antisecretory effect of serotonin: quantitation of release and site of action. 889 54

Mast cell activation-secretion by several signal transduction pathways results in the release of proinflammatory mediators including histamine, proteases, arachidonic acid metabolites and multifunctional cytokines. In the present investigations the activation-secretion responses of the cytokine-independent, cloned 10P2 cell line have been explored. [14C]Serotonin (5-HT) preloaded cells were stimulated with antigen, with and without IL-4, ionophore A23187, thapsigargin or phorbol myristate acetate (PMA). Following passive sensitization with anti-dinitrophenol (anti-DNP) IgE, mast cells released up to 31% of incorporated [14C]5-HT when stimulated with specific antigen (DNP-human serum albumin). This response was potentiated by pretreatment with IL-4. Significant degranulation (50%) was noted following treatment with calcium ionophore A23187, thapsigargin and ionophore A23187/PMA. Collectively, these results suggest that 10P2 cells undergo activation-secretion responses, assessed as degranulation of preloaded [14C]5-HT when challenged with IgE antigen, by influx of extracellular calcium or release of intracellular calcium stores, or by direct activation of protein kinase isozymes. As a growth factor-independent cell line, 10P2 cells may be a valuable adjunct to existing mast cell model systems currently used for pharmacologic investigations.
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PMID:Activation-secretion coupling in 10P2 murine mast cells challenged with IgE-antigen, ionophore A23187, thapsigargin and phorbol ester. 912 38

We developed a method for measuring the efflux of 5-hydroxytryptamine (5-HT, serotonin) from isolated intact granules of the mast cell of the beige mouse. This method combines electroporation of the vesicle membrane with amperometric detection of 5-HT. A single secretory granule is placed between two platinum electrodes (distance approximately 100 microm) and positioned adjacent (<1 microm) to a carbon fiber microelectrode. A short (approximately 30 micros) high-intensity voltage pulse (electric field of approximately 5 kV/cm) is delivered to the electrodes to trigger the mechanical breakdown of the granule membrane, which activates the release of 5-HT. We observed concurrent swelling of the granule matrix with the oxidation of 5-HT at the carbon fiber electrode (overpotential + 650 mV). Similar to the release of secretory products during exocytosis, the oxidation current exhibits a spike-like time course with a noninstantaneous rising phase (time between onset of current and maximum flux, t(max)) with approximately 25% of the molecules released during this period. When the current reaches its maximum, the granule matrix attains its maximum swollen state. We found that the rising phase depends on the initial cross-sectional area of the granule (t(max) approximately 21r2) and reflects the time required for membrane rupture. The average t(1/2)spike of the amperometric spikes was found to be approximately 150 ms, which is 3-7 times faster than the t(1/2) measured during cellular exocytosis.
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PMID:Kinetics of release of serotonin from isolated secretory granules. I. Amperometric detection of serotonin from electroporated granules. 928 83

We measured the efflux of 5-hydroxytryptamine (5-HT, serotonin) from an intact secretory granule extracted from the mast cell of the beige mouse. The efflux was measured with amperometry after rupture of the granule membrane was triggered by electroporation. We determined the diffusivity of 5-HT within the secretory granule to be 2.0 x 10(-8) cm2 s(-1) when the granule is in contact with a physiological saline and found that this diffusivity depends on the valence of the cation in the external electrolyte. There is a fivefold increase in the diffusion coefficient of 5-HT determined in CsCl (150 mM, pH 7.2) at 3.7 x 10(-8) cm2 s(-1) compared to that determined in histamine dihydrochloride (Hi, 100 mM at pH 4.5) at 0.7 x 10(-8) cm2 s(-1). We found that the rate of expansion of the granule matrix observed in physiological medium correlates with the efflux of 5-HT, and that the rate of swelling of the matrix and the efflux depend on the microviscosity within the granule matrix and not the bulk viscosity of the external solution. The low diffusivity of 5-HT (approximately 500-fold less than in the bulk), the observation that the valence of the counterion affects this diffusivity, and the relationship between the volume changes of the matrix and the efflux suggest that 5-HT is released from the granule by ion exchange. We discuss the implications of this result for exocytotic release in mast cells and propose that an ion exchange mechanism could control the rate of release in other secretory systems.
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PMID:Kinetics of release of serotonin from isolated secretory granules. II. Ion exchange determines the diffusivity of serotonin. 928 84

We examined the mechanism of the inflammatory response induced by topical application of mustard oil (0.5-20.0%/20 microliters per ear) to the mouse ear compared to that of the response to capsaicin. The dose-dependent increases in plasma extravasation and ear thickness reached a maximum at approximately 30 min after mustard oil application. Topical pretreatment of ears with capsaicin (250 micrograms/ear) diminished mustard oil-induced plasma extravasation for up to day 7 but not at day 14 after treatment. However, desensitization of the exudative response was not evoked by reapplication of mustard oil to ears. The inflammatory response to mustard oil did not differ between the ears of mast cell-deficient mice and those of the congenic normal mice. Mustard oil-induced plasma extravasation was unaffected by pretreatment with histamine H1 and 5-HT2 receptor antagonists and the capsaicin-functional inhibitor, ruthenium red, which inhibit capsaicin-induced ear oedema. The endopeptidase inhibitor, phosphoramidon, enhanced the ability of mustard oil to increase dye leakage. The tachykinin NK1 receptor antagonist, SR 140333 ((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pi peridin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2.2.]octane, chloride), not only inhibited mustard oil-induced plasma extravasation but also blocked the enhancement by phosphoramidon of the response to mustard oil. In contrast, the tachykinin NK2 receptor antagonist, SR 48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4,- dichlorophenyl)butyl]benzamide), and the tachykinin NK3 receptor antagonist, SR 142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4- phenylpiperidin-4-yl)-N-methylacetamide), had no effect on plasma extravasation. The present results demonstrated that mustard oil induces mouse skin inflammation through a mechanism different from that for capsaicin. Mediators such as histamine and 5-HT from mast cells appear to be minor factors in the response to mustard oil. In addition, evidence supports the assumption that the tachykinin NK1 receptor is involved in this model.
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PMID:Mechanism of mustard oil-induced skin inflammation in mice. 931 40


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