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)

There is now compelling evidence to incriminate bronchial mast cells in the pathogenesis of bronchoconstriction of allergic asthma. Human mast cells isolated from lung tissue or bronchoalveolar lavage release histamine and generate eicosanoids upon IgE-dependent activation. In this paper we present data that raise doubts about the significance of phospholipid methylation in IgE-dependent activation-secretion coupling and provide evidence that drugs such as 3-deazaadenosine inhibit mediator secretion by inhibiting phosphodiesterase, in addition to inhibiting putative methylation pathways. Activation of human mast cells and basophils also stimulates adenylate cyclase to increase levels of cyclic AMP, which, on the basis of pharmacological manipulation with purine nucleosides, we believe is involved in the progression of the secretory response. Human lung cells also generate both cyclo- and lipoxygenase products of arachidonate upon Ca++-dependent stimulation with complex interactions occurring between these pathways in the presence of the leukotriene inhibitor, Piriprost. The role of mast cells in the immediate airway response to inhaled allergens in asthma was demonstrated by showing an interaction between nonspecific bronchial reactivity and mast cell reactivity in predicting the airway response upon antigen inhalation. Further confirmation of this concept was obtained by showing an inverse relationship between the release of histamine and neutrophil chemotactic factor (NCF) into the circulation induced by antigen challenge, and nonspecific airway reactivity. The identification of significant increases in circulating mediators following antigen provocation of patients with seasonal asthma enabled the effects of drugs used in the treatment of asthma to be compared on airway calibre and mast cell mediator release. Sodium cromoglycate partially inhibited the airway and plasma histamine responses with antigen, but totally inhibited the increases in NCF. Salbutamol completely inhibited all responses, while ipratropium bromide, which produced the same bronchoconstriction as achieved with salbutamol, had no effect. The potent H1-antagonist astemizole partially inhibited bronchoconstriction without affecting histamine release. Antigen provocation produced a significant increase in circulating levels of the 13,14-dihydro-15-keto metabolite of PGF2 alpha which could originate from mast cell-derived PGD2. In both retrospective and prospective studies, a close relationship was shown between nonspecific bronchial reactivity and resting airway calibre in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationship between mediator release from human lung mast cells in vitro and in vivo. 240 26

Human dispersed lung cells containing 5-10% mast cells synthesised and released large quantities of prostaglandin D2 (PGD2) and thromboxane B2 (TXB2), with either IgE-dependent activation or ionophore A23187 challenge. The generation of these prostanoids and the release of histamine was related to the strength of activation stimulus. After activation the release of histamine and PGD2 proceeded in parallel, and the significant correlation between the release of these mediators suggests a common mast cell origin. This hypothesis is supported by cell enrichment experiments using Percoll density gradients. Prostaglandin D2 and histamine release was always associated with those fractions containing mast cells, whereas the generation of TXB2 was mainly associated with cells of the monocyte-macrophage series. The putative 5-lipoxygenase inhibitor 6,9-deepoxy-6, 9-(phenylimino)- 6,8-prostaglandin I1 (U-60,257, Piriprost) had complex inhibitory and potentiating effects on immunoreactive leukotriene C4 generation from ionophore activated human lung cells. The drug also had a surprising potentiating action on PGD2 release, while simultaneously inhibiting the generation of TXB2. The release of prostanoids from human lung cells is discussed in relation to the putative role of prostaglandins in asthma, with particular emphasis on the pharmacological actions of PGD2 on human airway function in vivo.
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PMID:The generation of prostaglandins by human lung and their effects on airway function in man. 351 76