Mast cell leukotrienes

The structure-activity relationships for thiourea derivatives have been investigated as vanilloid receptor antagonist,216 220 and mast cell leukotriene release, etc.221 224... 

Malaviya R, Abraham SN Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis. J Leukoc Biol 2000 67 841-846. 

Along with the bronchodilators, several types of dragp are effective in Hie treatment of asthma. These include corticosteroids, leukotriene formation inhibitors, leukotriene receptor agonists, and mast cell stabilizers. 

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... 

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]. 

Th2 lymphocytes are one of the primary factors initiating and perpetuating the inflammatory response.7 In addition, proinflammatory mediators such as the leukotrienes generated during mast cell degranulation can increase vascular permeability, leading to airway edema and increased mucus production.8 Eosinophilic infiltration of the airways is a hallmark of asthma, and activated eosinophils can cause bronchoconstriction and AHR.9... 

Antihistamines and intranasal corticosteroids are considered first-line therapy for allergic rhinitis, whereas decongestants, mast cell stabilizers, leukotriene modifiers, and systemic corticosteroids are secondary treatment options. 

Pharmacotherapy has an important role in managing AR symptoms (Table 59-2). Intranasal corticosteroids, systemic and topical antihistamines and decongestants, mast cell stabilizers, and immunotherapy all are beneficial in treating symptoms of AR.9 Antihistamines and intranasal corticosteroids are considered first-line therapy for AR, whereas decongestants, mast cell stabilizers, leukotriene modifiers, and systemic corticosteroids are secondary treatment options10-12 (Fig. 59-2). Whenever exposure to allergens can be predicted (e.g., SAR or visiting homes with a pet), medications should be used pro-phylactically to maximize effectiveness.11... 

Bronchoconstriction is also elicited by several endogenous chemicals released from mast cells during an allergy or asthmatic attack. These substances, including histamine and the leukotrienes, may also promote the inflammatory response and edema formation. 

Although it appears that severe IL-4-regulated enteropathy is not required for immune expulsion of T. spiralis, it is still possible that Th2 cytokines can act in a direct fashion to create an environment unfavourable for intestinal parasites. It remains to be shown directly whether these effects are sufficient to expel parasites. Indeed, there is considerable evidence to support a variety of pathophysiological effects of IL-4 and/or TNF on the gut. These effects may be mediated by factors including cytokines and mast-cell products (e.g. leukotrienes and 5-hydroxytryptamine). 7. spiralis infections result in increased fluid and mucus secretion into the lumen as well as increased intestinal propulsive activity and more rapid intestinal transit (Castro et al, 1979 Russell, 1986 Vermillion and Collins, 1988 Vermillion et al., 1991 Weisbrodt et al, 1994 Barbara et al, 1997). The increased contractility of radial and longitudinal muscle is greater in high-... 

Perdue, M.H., Ramage,J.K., Burget, D., Marshall, J. and Masson, S. (1989) Intestinal mucosal injury is associated with mast cell activation and leukotriene generation during Nippostrongylus-induced inflammation in the rat. Digestive Disease Science 34, 724—731. 

At the cellular level, eosinophils, mast cells, alveolar macrophages, lymphocytes and neutrophils recruited to the airways of asthmatics produce a variety of inflammatory mediators, such as histamine, kinins, neuropeptides, and leukotrienes, which lead to airway smooth muscle constriction and obstruction of airflow, and the perpetuation of airway inflammation [20, 21]. An understanding of the inflammatory processes and the molecular pathways of these mediators has led to the development and widespread use of several pharmacologic agents that mitigate airway inflammation and bronchoconstriction. 

Mast cell degranulation in response to allergens results in release of mediators such as histamine eosinophil, and neutrophil chemotactic factors leukotrienes C4, D4, and E4 prostaglandins and platelet-activating factor (PAF). Histamine is capable of inducing smooth muscle constriction and bronchospasm and may play a role in mucosal edema and mucus secretion. 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Figure 4.1. Model of neurogenic inflammation. Stimulation at the skin initiates orthodromic impulses in sensory nerve receptors which elicit antidromic impulses in branching collaterals. The release of neuropeptides such as calcitonin gene-related peptide (CGRP), substance P (SP), and somatostatin (SOM) from nerve terminals ensues and they in turn stimulate the release of histamine (H) and the generation of leukotrienes (LT) from nearby mast cells. These mediators then produce vasodilatation and an increase in vascular permeability. In addition, they act on the nerve terminal to produce further...

Stimulation by thrombin does not lead to the generation of leukotriene C4 or B4, whereas stimulation of the same mast cells by the calcium ionophore, A23187, does. The secretory response elicited by thrombin is prevented by preincubation with AT-III, a plasma inhibitor of thrombin, or by hirudin, a thrombin inhibitor derived from the leech [135],... 

Figure 4.8. Hypothesis for the local generation of mast-cell-stimulating peptides by the action of neutrophil-derived enzymes on albumin. Initial stimulation of the mast cell by any of a variety of agents causes the release of preformed histamine (H) neutrophil and eosinophil chemotactic factors (NCF, ECF) and enzymes and the de novo synthesis of prostaglandins (PG) and leukotrienes (LT). These agents increase vascular permeability and vessel diameter. As a result, albumin and later neutrophils (PMN) enter the tissue space where the latter undergo phagocytosis and the secretion of proteolytic enzymes to the extracellular space where they act on albumin to generate NRP (neurotensin-related peptide) and HRP (histamine-releasing peptide). These newly formed peptides then act as a second stimulus to the mast cell. In addition NRP and HRP may affect other immunocompetent celt such as monocytes, macrophages or eosinophils.

Serotonin Mast cells, basophils Contraction of smooth muscle leukotriene... 

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