Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanisms of relaxation and contraction to protease-activated receptor- (PAR) tethered ligand peptides (SFLLRN/TFLLR, SLIGRL and GYPGKF (all C-terminally amidated) for PAR1, PAR2 and PAR4, respectively) and enzymes (thrombin and trypsin) were investigated in isolated segments of rat trachea, main and first order intrapulmonary bronchi. In airway segments previously exposed to SLIGRL, SFLLRN caused contractions that were potentiated by indomethacin, but were independent of mast cell degranulation. Contractions to TFLLR in the intrapulmonary bronchi were similarly potentiated by indomethacin. SLIGRL caused epithelium-dependent relaxations which were unaffected by N(G)-nitro-L-arginine, 1-H-oxodiazol-[1,2,4]-[4,3-a]quinoxaline-1-one or zinc-protoporphyrin-IX but were abolished by haemoglobin in all three regions of the airways. Relaxations to SLIGRL were markedly attenuated by indomethacin only in the main and intrapulmonary bronchi. GYPGKF caused epithelium-dependent relaxations in all three regions of the airway which were only significantly inhibited by indomethacin in the intrapulmonary bronchi. In general, thrombin and trypsin failed to cause any response in the airways tested. Intense PAR2-immunoreactivity was observed on airway epithelium. PAR1-immunoreactivity was faint on airway epithelium and smooth muscle, but was prevalent in mast cells. These findings indicate that PAR2 and possibly PAR4 present on rat airway epithelia mediate smooth muscle relaxation via cyclo-oxygenase-dependent and -independent mechanisms. PAR1-mediated contractions were most likely due to activation of smooth muscle receptors. The general failure of thrombin and trypsin to cause responses which may have been due to endogenous protease inhibitors, highlights the need for caution in assessing pathophysiological roles for PARs if only enzymes are used to activate PARs.
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PMID:Effect of protease-activated receptor (PAR)-1, -2 and -4-activating peptides, thrombin and trypsin in rat isolated airways. 1113 35

Proteinase-activated receptor-2 (PAR2) belongs to a new G protein-coupled receptor subfamily activated by serine proteinases. PAR2 has been demonstrated to play a role during inflammation and immune response in different tissues including the skin. We examined whether PAR2 is functionally expressed by cutaneous human primary skin mast cells (HPMC) and the human mast cell line 1 (HMC-1). Reverse transcription-polymerase chain reaction and FACS analysis show expression of PAR2 both at the RNA and protein level. HPMCs and HMC-1 also express PAR1, PAR3, and PAR4. Ca-mobilization studies demonstrate functional PAR2 expressed by human skin mast cells, as shown by natural and synthetic PAR2 agonists. PAR2 agonists induced histamine release from HPMC indicating a role of PAR2 in regulating inflammatory and immune responses by skin mast cells. Double-immunofluorescence staining reveals colocalization of PAR2 with tryptase in the majority of human skin mast cells. In conclusion, trypsin and tryptase as well as specific agonists for PAR2 were able to induce Ca2+ mobilization in HPMCs, and agonists of PAR2 induce the release of histamine from these cells. Thus, PAR2 may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity.
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PMID:Functional characterization and expression analysis of the proteinase-activated receptor-2 in human cutaneous mast cells. 1647 Jan 80

Activated protein C (APC) regulates the functional activity of mast cells by reducing release of beta-hexosaminidase, the marker of mast cell degranulation. APC could modulate the cell secretion of both: the rest mast cells and the activated cells with degranulators, such as proteinase-activated receptor agonist peptide (PAR1-AP) and compound 48/80. PAR1 desensitization with thrombin abolishes the effect of low APC concentration (< or =1,5 nM) on beta-hexosaminidase release by mast cells. APC, inactivated with phenilmethylsulfonilftoride (PMSF), did non mimic the enzyme action on mast cells. The duodenal proteinase, duodenase, activates the peritoneal mast cell via PAR1. APC abolishes the proinflammatory action of duodenase and PAR1-AP by means of reducing release of mast cell mediators. Pretreatment of mast cell with L-NAME abolished these APC effects. Thus, APC-induced decrease of mediator release could be attributed to NO generation by mast cells. Our data indicate that PAR1 takes part in the mechanism of regulatory anti-inflammatory APC action.
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PMID:[The role of PAR1 in the protective action of activated protein C in the non-immune mast cell activation]. 1803 22

This paper summarizes the current knowledge on the interactions between intestinal mast cells, enteric neurons and visceral afferents which are part of the gut brain axis. The focus of this review is on the relevance of the mast cell-nerve axis in the human intestine. Similarities and important differences in the organization of the mast cell-nerve axis between human and rodents are discussed. Functionally important human mast cell mediators with neural actions in the human ENS are histamine (H1-4 receptors), proteases (PAR1 receptors), several cytokines and chemokines and probably also serotonin (5-HT(3) receptors). On the other hand, mediator release from human intestinal mast cells is modulated by neuropeptides released from enteric and visceral afferent nerves. This article is part of a Special Issue entitled: Mast Cells in Inflammation.
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PMID:Mast cell-nerve axis with a focus on the human gut. 2170 3

Thrombin, a key player in coagulation, is widely held to induce and promote inflammation. As of now, the features, kinetics and control of thrombin's proinflammatory effects on the skin remain to be characterized in detail. We, therefore, injected thrombin into the ear skin of mice and observed strong, dose-dependent and transient ear swelling responses as well as mast cell (MC) degranulation. Unexpectedly, thrombin induced even stronger, not reduced, ear swelling in MC-deficient KitW-sh/W-sh mice. Prior local reconstitution of KitW-sh/W-sh mice with MCs inhibited this effect, indicating that MCs may contribute to the control of thrombin-induced skin inflammation. In line with previous studies, we found that MCs express the thrombin receptors PAR1, PAR3 and PAR4, thrombin induces direct and dose-dependent MC degranulation, and that degranulated MCs inactivate thrombin. Further findings suggested that MC-mediated protection from thrombin-induced inflammation is likely to rely on the effects of MC proteases. We show for the first time that MC-deficient mice and MC protease 4-deficient mice with normal numbers of MCs show markedly increased ear swelling in response to thrombin as compared to wild-type mice. Taken together, these results suggest that thrombin-induced skin inflammation is controlled, in part, by MC protease 4 released from activated MCs. For MC-driven diseases such as chronic spontaneous urticaria, which has been linked to increased thrombin generation, this might mean that MCs may contribute to the resolution of skin inflammatory responses.
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PMID:Mast cells are critical for the limitation of thrombin-induced skin inflammation. 2878 94