Mast cells inflammatory responses

While the findings in mice are of interest, it is important to note that there are four known mammalian adenosine receptors and that the pattern of adenosine receptor expression on mast cells (as well as other immime cells and/or structural cells), and the regulation of their expression by such cells (e.g., during inflammatory responses), which can represent major determinants of adenosine responses, vary substantially among species [70-72]. For example, it is thought that adenosine-induced broncho-constriction is mediated by adenosine A1 and A2B receptors in rats and mice, A3 receptors in rats, guinea-pigs and mice, and A2B receptors in humans [72]. 

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... 

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... 

Inflammation is present in the lungs of all smokers. It is unclear why only 15% to 20% of smokers develop COPD, but susceptible individuals appear to have an exaggerated inflammatory response.5 O The inflammation of COPD differs from that seen in asthma, so the use of anti-inflammatory medications and the response to those medications are different. The inflammation of asthma is mainly mediated through eosinophils and mast cells. In COPD the primary inflammatory cells include neutrophils, macrophages, and CD8+ T lymphocytes. 

Immunoglobulin receptors, such as the high affinity receptor for IgE, are present on mast cells and bloodbome basophils. These receptors play an important role in hypersensitivity and the initiation of acute inflammatory responses. 

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. 

Upon activation, mast cells release numerous mediators, including vasoactive amines, proteases, pro-inflammatory cytokines (e.g. IL-ip, IL-6, IL-18 and TNF-a) and also regulatory Th2 cytokines (e.g. IL-4, IL-10 and IL-13) (Burd et al., 1989 Gordon and Galli, 1990 Marietta el al., 1996 Toru et al., 1998 Aoki et al., 1999 Lorentz et al, 2000). Therefore, the mastocytosis in the infected mucosa represents an immunopathological rather than a protective response. Indeed, our studies have shown that expulsion of T. spiralis from TNF-Rl / or iNOS / mice was achieved in the absence of a substantial mastocytosis and subsequent amelioration of enteropathy (Lawrence etal., 1998, 2000). 

Dietary copper deficiency increases the acute inflammatory response in rats and other small laboratory animals (Schuschke et al. 1994). The release of inflammatory mediators, such as histamine and serotonin, from mast cells increases the vascular permeability of postcapillary venules and results in edema. In copper-deficient rats, release of histamine from mast cells correlates positively with frequency of the acute inflammatory response. Copper-deficient rats (0.6 mg Cu/kg DW ration for 4 weeks) have more mast cells in muscle than copper-adequate controls given diets containing 6.3 mg Cu/kg DW ration however, histamine content of mast cells is not affected (Schuschke et al. 1994). An early clinical sign of copper deficiency is a reduction in the number of circulating neutrophils the mechanism for copper-deficient neutropenia (leukopenia in which... 

From 4 to 8 hours after the initial exposure to an allergen, a late-phase reaction may occur, which is thought to be due to cytokines released primarily by mast cells and thymus-derived helper lymphocytes. This inflammatory response likely is responsible for persistent, chronic symptoms including nasal congestion. 

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