Mast cells mechanism

Immunologic triggers that contribute to AD development include food allergens and aeroallergens. A variety of allergens cause approximately 85% of AD patients to demonstrate an immediately positive skin test of serum IgE antibody However, AD is not a purely IgE-type of condition, as this would indicate presence of an immediate hypersensitivity mast-cell mechanism. 

Cromones suppress the release of mediators from mast cells by a mechanism that is not known (Fig. 4). In order to achieve the complete suppressive effect, cromones have to be given prophytactically several days to weeks before exposure to seasonal allergens can be expected,... 

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

Cromones are used to prevent asthma attacks. To be effective they have to betaken continuously. Their mechanism of action is poorly understood. Cromones (cromolyn sodium, nedocromil) act as mast cell-stabilizing agents,... 

There are also other immimological mechanisms, especially via IgG or IgM antibodies with immune complex formation, which can lead to similar clinical conditions [20, 34, 42] as has been shown in dextran anaphylaxis (table 1). Triggering of mast cells and basophils leads to release of various vasoactive mediators, among which histamine was the first recognized in 1908 (fig. 3,4) [6]. 

This chapter highlights the mechanisms responsible for mast cell activation during anaphylactic responses to environmental substances. In addition to discussing in detail the activation of mast cells and basophils by IgE and antigen, we also will describe how mouse models have been used to analyze the importance of various proteins, cells, mediators and activation mechanisms in the expression of anaphylaxis in that species. 

Although human anaphylaxis is a systemic reaction, the mouse model of passive cutaneous anaphylaxis (PGA) has been used extensively to enhance our understanding of mechanisms which also may contribute to systemic anaphylaxis. Unlike systemic anaphylaxis in the mouse, PGA appears to be entirely dependent on mast cells [4,6]. While IgE appears to be the primary antibody isotype that mediates PCA reactions in actively immunized mice, activation of FcyRIII by a fraction of IgGl antibodies (called anaphylactic IgGl) can also mediate PCA reactions in mice [4]. 

Gilfillan AM. Peavy RD. Metcalfe DD Amphfication mechanisms for the enhancement of antigen-mediated mast cell activation. Immunol Res 2008. 38... 

Few prospective studies of induced anaphylaxis have been performed in human subjects to imderstand the molecular basis of systemic anaphylaxis, because of the potentially rapid, Ufe-threatening outcome. Accordingly, various models of anaphylaxis have been estabUshed in laboratory animals, particularly mice, and extensively studied to clarify the underlying mechanisms. Such studies revealed that the classical pathway utilizing mast cells, IgE and histamine cannot explain all cases of anaphylaxis. 

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]. 

Physical factors, such as heat, mechanical stimulation and exercise, may sometimes lead to mast cell degranulation and whealing in the skin, but rarely provoke systemic anaphylaxis [4, 26]. Patients do report that these and other factors in combination (such as exercise, heat and alcohol) may elicit anaphylaxis in summation. 

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

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... 

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