Mast cells mediators released

Table 4. Triggers for mast cell mediator release ... 

No increase of plasma leukotrienes after RCM administration Mast cell mediator release correlates with severity of reaction, positive basophil activation test to RCM in patients... 

Cromolyn and nedocromil are inhaled anti-inflammatory agents that block both the early- and late-phase response. Both agents are considered alternative therapies to inhaled corticosteroids for the treatment of mild persistent asthma however, both are less effective than low doses of inhaled corticosteroids.2,30 The exact mechanism of action of these agents is not understood, but they appear to inhibit mast cell mediator release as well as modulate other inflammatory responses.3... 

Theophylline appears to produce bronchodilation by inhibiting phosphodiesterases, which may also result in antiinflammatory and other nonbronchodilator activity through decreased mast cell mediator release, decreased eosinophil basic protein release, decreased T-lymphocyte proliferation, decreased T-cell cytokine release, and decreased plasma exudation. 

Charlesworth EN, Kagey-Sobotka A, Norman PS, Lichtenstein LM. Effect of cetirizine on mast cell-mediator release and cellular traffic during the cutaneous late-phase reaction. J Allergy Clin Immunol 1989 83(5) 905-12. 

Taken together, the identification of mast cell hyperplasia and mediator release at sites of tissue fibrosis and wound healing, observations in animal models, and study of the actions of mast cell products, has provided much circumstantial evidence that mast cells are involved in tissue remodelling, healing and fibrosis. It is unlikely that mast cells are essential in these responses, but more likely that they augment them. Complex interactions between different connective tissue components, mast cells and other inflammatory cells are likely to operate, and are unlikely to be fully delineated in humans in vivo. It seems reasonable to hypothesize however that initial mast cell mediator release has the potential to activate fibroblasts, which may then promote the recruitment at d proliferation of further mast cells, explaining the mast cell hyperplasia often witnessed at sites of chronic inflammation. 

Fig. 2. IgG-mediated systemic versus local anaphylaxis, a IgG-mediated systemic anaphylaxis. When allergen-IgG immune complexes are formed in the circulation, basophils immediately capture them through IgG receptors on their surface and are activated to release PAF, that in turn act on vascular endothelial cells, leading to increased vascular permeability, b Passive cutaneous anaphylaxis. When allergen-IgG immune complexes are formed in the skin, they stimulate tissue-resident mast cells to release chemical mediators such as histamine, leading to local inflammation. 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

Corticosteroids (e.g., beclomethazone, flunisolide, triamcinolone) have anti-inflammatory and immunosuppressant actions. These drugs are used prophylactically to prevent the occurrence of asthma in patients with frequent attacks. Because they are not useful during an acute attack, corticosteroids are prescribed along with maintenance bronchodilators. These drugs are also administered by inhalation. Cromolyn is another anti-inflammatory agent used prophylactically to prevent an asthmatic attack. The exact mechanism of action of cromolyn is not fully understood however, it is likely to involve the stabilization of mast cells. This prevents the release of the inflammatory mast cell mediators involved in inducing an asthmatic attack. Cromolyn has proven effective in patients with exercise-induced asthma. 

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

The answers are 25-e, 26-b, 27-a. (Hardmanr pp 67—68. Katzung, pp 30, 134.) Anaphylaxis refers to an acute hypersensitivity reaction that appears to be mediated primarily by immunoglobulin E (IgE). Specific antigens can interact with these antibodies and cause sensitized mast cells to release vasoactive substances, such as histamine. Anaphylaxis to penicillin is one of the best-known examples the drug of choice to relieve the symptoms is epinephrine. 

Intranasal corticosteroids effectively relieve sneezing, rhinorrhea, pruritus, and nasal congestion with minimal side effects (Table 79-4). They reduce inflammation by blocking mediator release, suppressing neutrophil che-motaxis, causing mild vasoconstriction, and inhibiting mast cell-mediated, late-phase reactions. 

Inhibitors of histamine release One of the effects of the so-called mast cell stabilizers cromoglycate (cromolyn) and nedocromil is to decrease the release of histamine from mast cells (p. 72, 326). Both agents are applied topically. Release of mast cell mediators can also be inhibited by some Hi antihistamines, e.g., oxatomide and ketotifen, which are used systemically. 

Albeturol sulfate 32.5 (1.5) 41.7 (1.5) 40.0(1.7) A selective beta-2 agonist broncbodilator that inhibits the release of mast cell mediators and increases clearance of the mucus membranes. 

The response of mast cells includes release of arachidonic acid due to membrane PhL A2 activation following a ligand-induced increase in cellular Ca2+. PTX reduces the Ca2+-mediated GTP S-dependent release of this fatty acid in permeabil-ized cells [102,103]. This raised the possibility of a direct link, not only between receptors and PhL C, but also between receptors and PhL A2. Existence of a G protein-mediated. PTX-sensitive, activation of PhL A2 independent of G protein-mediated activation of PhL C was confirmed in studies first with fibroblasts [104] and then with FRTL thyroid cells [105]. Studies with the latter cells show that a,-adrenergic receptors promote arachidonic acid release [105] and that this effect is mimicked in permeabilized cells by GTP and is not blocked by inhibition of PhL C with neomycin. Thus, at least two Gp proteins need to be defined a Gp-stimu-lating PhL C (Gp(c) and a Gp-stimulating PhL A2 (Gp,a). It is possible that rat brain G is PTX-sensitive Gplc. 

Mast cell stabilizers. Cromoglycate (cromolyn) and nedocromil decrease, by an as yet unknown mechanism, the capacity of mast cells to release of histamine and other mediators during allergic reactions. Both agents are applied topically (p.338). 

Stabilization of mast cells. Cromolyn prevents IgE-mediated release of mast cell mediators, although only after chronic treatment. It is applied locally to conjunctiva, nasal mucosa, the bronchial tree (inhalation), and intestinal mucosa (absorption is almost nil with oral intake). Indications prophylaxis of hay-fever, allergic asthma, and food allergies. Nedocromil acts similarly. 

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