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)

This study has examined the metabolism of arachidonic acid in the mouse bone marrow-derived mast cell (BMMC) during immunologic and nonimmunologic activation. The predominant pools of endogenous arachidonate in the mast cells were found in ethanolamine (46%), choline (39%) and inositol (14%) containing glycerolipids. Initial studies established conditions where equilibrium labelling of these major phospholipids in the BMMC could be reached. Upon challenge, arachidonate was lost from all major phospholipid classes (phosphatidylethanolamine greater than phosphatidylcholine greater than phosphatidylinositol). There was a small but significant increase in the amount of label associated with phosphatidic acid during cell activation. Arachidonate was distributed among 1-acyl, 1-alkyl and 1-alk-1-enyl-linked subclasses of PC and PE. The rank order of loss of labelled arachidonate from the major PE and PC subclasses during antigen and ionophore activation was 1-alk-enyl-2-arachidonoyl-GPE greater than 1-acyl-2-arachidonoyl-GPC greater than 1-acyl-2-arachidonoyl-GPE greater than 1-alkyl-2-arachidonoyl-GPC. Labelled products released into the supernatant fluids and free arachidonic acid within the cell accounted for the bulk of arachidonate lost from phospholipids. Labelled products in the supernatant fluids were composed of LTB4, LTC4, PGD2 and free arachidonic acid. BMMC phospholipids were also labelled for 24 hr with [3H]choline, [3H]myoinositol or [14H]ethanolamine and labelled 2-lyso phospholipids were measured after cell activation. Radioactivity in lysophospholipids from PC, PE and PI increased significantly between 30 s and 2 min after antigen activation and then declined. Taken together, these studies suggest that arachidonate is mobilized predominantly from PE and in particular 1-alk-1-enyl-2-arachidonoyl-GPE by the direct removal of arachidonate from the sn-2 position of the molecule. Most of this arachidonate is then released from cells as eicosanoids or free fatty acid.
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PMID:Arachidonic acid metabolism during antigen and ionophore activation of the mouse bone marrow derived mast cell. 189 88

The synthesis of platelet-activating factor (PAF) and of the 1-acyl analogue of PAF, 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-2-acetyl-GPC) was examined in seven human cell preparations (lung mast cell, basophil, endothelial cell, neutrophil, eosinophil, lung macrophage, platelet) and in human lung fragments. Cells were activated by either an appropriate receptor-mediated stimulus or by ionophore A23187 in the presence of [3H]acetate. All cell types, with the exception of the platelet, responded to stimulation with at least a twofold increase in the formation of labeled 1-radyl-2-acetyl-GPC as compared with control values. A23187 was the more potent stimulus in all cell types examined except the lung mast cell, in which anti-IgE consistently induced the synthesis of more 1-radyl-2-acetyl-GPC. Human lung fragments stimulated by anti-IgE, Ag Amb a I (after passive sensitization), or A23187 also incorporated [3H]acetate into 1-radyl-2-acetyl-GPC. Subclass analysis of 1-radyl-2-acetyl-GPC produced by each cell indicated that the cell types examined can be divided into two groups according to the predominant type of 1-radyl-2-acetyl-GPC produced. Some cell types (mast cell, basophil, endothelial cell) produced predominantly 1-acyl-2-acetyl-GPC, whereas others (neutrophil, eosinophil, lung macrophage) produced almost exclusively PAF. In some cell types, such as the lung mast cell and the basophil, A23187 stimulation increased the synthesis of PAF relative to 1-acyl-2-acetyl-GPC as compared with anti-IgE stimulation. In the lung fragments, [3H]acetate was predominantly incorporated into 1-acyl-2-acetyl-GPC upon IgE-mediated stimulation (anti-IgE, Amb a I) and into PAF upon A23187 stimulation. The differential production of these two phospholipids was confirmed by determining their sensitivity to lipase A1 and phospholipase A2 hydrolysis and by HPLC. These data demonstrate that 1-acyl-2-acetyl-GPC can be synthesized by a variety of human cells involved in the inflammatory reaction. This finding raises fundamental questions about the biologic role of this molecule and the factors regulating its synthesis within inflammatory cells.
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PMID:Differential synthesis of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine and platelet-activating factor by human inflammatory cells. 207

The main concerns in anterior segment therapy are allergy, inflammation and infection. Allergic reactions can be divided into four types with differing etiologies. Although all types may be manifested in ocular inflammatory states, Type I, involving the release of histamine is probably the most common, being involved in responses to pollen, drugs and in GPC and VKC. Inflammation is a complex, multicomponent, protective response involving the synthesis, release and actions of many chemical mediators, including prostaglandins which are synthesised from cell membrane components. Drugs used act through a number of mechanisms: decongestants act directly on dilated vessels to cause constriction and decreased permeability; antihistamines block the access of histamine to its receptors in the target tissues and mast cell stabilisers prevent the release of mediators including histamine in response to the antigen/antibody interaction. Both the non-steroidal anti-inflammatory drugs and steroids decrease the production of the prostaglandins by inhibiting the action of cyclo-oxygenase and phospholipase respectively. Most infections are bacterial and the majority of drugs used are antibacterial. However, many of the principles of antibacterial therapy can be applied to the other classes of drugs. The basic principle in the treatment of any infection is that of selective toxicity, which is the ability to effect harm to the infecting cells (e.g. bacteria) without a similar effect being exerted on the host cells. This selectivity may be qualitative, at no drug concentration is the host cell affected in the same way as the invading cell, or quantitative where the separation of effect is dose dependent. The selectivity may have a biochemical or distributional basis, and the effects may be, in the case of bacteria, bactericidal or bacteriostatic. Most antibiotics used in anterior segment therapy show quantitative biochemical selectivity and are bacteriostatic in action. The antiviral compound (aciclovir) shows quantitative biochemical selectivity because it is a pro-drug activated in infected cells.
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PMID:The pharmacological basis of anterior segment therapy. 969 27

Leukotrienes have been shown to play a role in the pathogenesis of ocular inflammatory and allergic reactions like vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis. This study was designed to determine leukotriene B4 (LTB4) and leukotriene C4 (LTC4) levels in the tears of patients with ocular prosthesis-associated giant papillary conjunctivitis (OP-GPC) and to evaluate the effects of lodoxamide 0.1% on tear LTB4 and LTC4 levels of OP-GPC patients. Tear LTB4 and LTC4 levels were determined by an ELISA technique in the tears of ten OP-GPC patients before and after treatment with lodoxamide 0.1% for one month. The results were compared with that of ten healthy control subjects. The mean tear LTB4 and LTC4 levels of the OP-GPC patients were significantly higher than those of the control group. After treatment with lodoxamide 0.1%, tear LTB4 and LTC4 levels of the OP-GPC patients decreased significantly. This is the first report of elevated LTB4 and LTC4 levels in tears of OP-GPC patients and it points to the possible role of leukotrienes in the immunopathogenesis of OP-GPC. The results also indicate that lodoxamide 0.1%, a mast cell membrane stabilizer, is effective in significantly reducing tear LTB4 and LTC4 levels in OP-GPC patients.
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PMID:Effect of lodoxamide on tear leukotriene levels in giant papillary conjunctivitis associated with ocular prosthesis. 978 8

Atopic ocular diseases involve a spectrum of immuno-inflammatory responses. There are minimal pathologic changes with SAC. With PAC, there is increased mast cell activation and late-phase inflammatory cell infiltrate as a consequence of continued allergic stimulation. Associated with the more chronic and severe forms of atopic ocular disorders, GPC, VKC and AKC, there is persistent mast cell, eosinophil, and lymphocyte activation resulting in pathologic changes. Therapeutic intervention for atopic ocular diseases has focused on symptomatic improvement. However, with an increasing understanding of the molecular mechanisms associated with the allergic inflammatory response, experimental studies may facilitate the development of preventative strategies.
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PMID:Atopic ocular disease. 1206 72

Ocular allergic disorders can be a component of systemic or local allergies. The importance of ocular allergy results from its incidence rather than from its severity, however, some of them are vision-threatening. The majority of ocular allergies affect the conjunctiva, eyelids and sometimes cornea that is exposed to the environment and is the place of interaction between allergens and immunocompetent cells. Different types of allergic disorders in the eye may have similar signs and symptoms, but each has its own pathognomonic characteristics, which help to diagnose, differentiate and choose the most suitable therapy. Ocular allergic diseases are classified into six categories: SAC, PAC, VKC, AKC, GPC and ConBC. In 2001 EAACI suggested new classification, also of allergic conjunctivitis, into IgE-mediated and non-IgE-mediated conjunctivitis. IgE-mediated conjunctivitis may be divided into intermittent and persistent conjunctivitis. Persistent allergic conjunctivitis is classified into vernal and atopic keratoconjunctivitis. Conjunctivitis contact allergy is a non-IgE form of allergic conjunctivitis. Currently available medications provide safe and effective management of most cases of ocular allergy. Drugs used in the treatment of ocular allergic disorders include mast cell stabilizers, antihistamines, steroids, NSAID's, artificial tears and others.
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PMID:[Clinical picture, diagnosis and therapy of allergic eye diseases]. 1452 17