Mast cells development

Watanabe, N., Nawa, Y., Okamoto, K. and Kobayashi, A. (1 994) Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or of mast cell development. Parasite Immunology 1 6, 1 37-144. 

Figure 32.9. Schematic representation of Type I hypersensitivity. Induction Resident respiratory tract dendritic cells (DC) take and process antigen, mature, migrate to the draining lymph nodes, and present antigen to T lymphocytes. Activated T-lymphocytes, in turn, activate B-cell differentiation into antibody-producing plasma cells. IL-4 promotes Ig isotype class switching from IgM to IgE and promotes mast cell development. IgE is associated with mast cells. Elicitation Allergen crosslinks the mast-cell-bound IgE, thereby causing the release of preformed mediators and cytokines. (See Table 32.7.) Inflammation and bronchoconstriction occur.

Galli, S.J. (1990). New insight into the riddle of the mast cells microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab. Invest. 62, 5-33. 

Quakenbush, E. J., Wershil, B. K., Aguirre, V., and Gutierrez-Ramos, J. C. (1998). Eotaxin modulates myelopoiesis and mast cell development from embryonic hematopoietic progenitors. Blood 91, 1887-1897. 

In contrast to the Miyajima et al. (34) report of FceRI-independent induction of anaphylaxis, Dombrowicz et al. (45) showed that FceRI is requisite for the induction of anaphylaxis. Lack of FceRI did not affect mast cell development, nor did it affect the half-life of IgE. FceRI receptor-deficient mice were protected from anaphylaxis and had no tachycardia, body temperature drop, or Evans Blue... 

Syk and ZAP-70 are early intermediates in the transduction of signals from immune receptors, including the B- and T-cell recqrtors for antigen, activatory natural killer-cell receptors, the mast cell and basophil receptor for IgE, and the widely distributed receptors for the Fc portion of IgG. Immune receptors control checkpoints in lymphocyte development and serve to integrate the responses of innate and acquired immunity. 

Adding another layer of complexity to the regulation of mast cell activation levels in vivo is the observation that activated mast cells can respond to, and in some cases produce, a myriad of mediators that may serve to amplify FceRI-induced responses. For example, stem cell factor (SCF), the ligand for KIT, both can enhance FceRI-dependent activation of mouse or human mast cells and, under certain circumstances, can directly induce mast cell degranulation [6, 25, 62]. Thus, elevated SCF levels and/or activating KIT mutations (such as those that occur in mastocytosis) may exacerbate mast cell-driven reactions. Indeed, patients (both adult and children) with extensive skin disease associated with mastocytosis are at increased risk to develop severe anaphylaxis [63]. Moreover, it was recently reported that cases of idiopathic anaphylaxis are... 

Kalesnikoff J, Galli SJ New developments in mast cell biology. Nat Immunol 2008 9 1215-1223. 

H, Nishioka K, Hirokawa K, Etori M, Yamashita M, Kubota X Minegishi Y, Yonekawa Y, Karasuyama H Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity 2005 31 23 191-202. 

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]. 

Mastocytomas and diffuse cutaneous mastocytosis are further manifestations of cutaneous mastocytosis (CM) [9]. Solitary mastocytomas are common in children. Most are present at birth or develop in infancy. These lesions are flat or mildly elevated, well demarcated, solitary yellowish red-brown plaques or nodules, typically 2-5 cm in diameter. Diffuse cutaneous mastocytosis is a rare disorder characterized by diffuse mast cell infiltration of large areas of the skin that presents in infants in the first year of life. Severe edema and leathery indurations of the skin leads to accentuation of skin folds (pseudo-lichenified skin) and a peau-dbrange-like appearance. Systemic complications include hypotension and gastrointestinal hemorrhage. Infants and young children with considerable mast cell infiltration of the skin sometimes exhibit blister formation in the first 3 years of life. MPCM and other forms of CM have been classified in a consensus nomenclature (table 1) [10]. 

Two immunoassays have been developed to measure tryptase in human fluids, one that measures mature a/(3-tryptases, i.e. total tryptase, available commercially, and one developed by Schwartz et al. [7] that measures both mature (3-tryptase and immature a/(3-tryptases. This distinction is of clinical relevance since immature tryptases reflect mast cell burden whereas mature tryptases indicate mast cell activation. Thus, for the diagnosis of anaphylaxis it would be extremely important to be able to differentiate between acute anaphylaxis and increases in tryptase due to increase in numbers of mast cells as happens in mastocytosis. Total tryptase would be high in both conditions, whereas mature tryptase will be only high in anaphylaxis but negligible in mastocytosis. 

Foster B, Schwartz LB, Devouassoux G, Metcalfe DD, Prussin C Characterization of mast-cell try-ptase-expressing peripheral blood cells as basophils. J Allergy Clin Immunol 2002 109 287-293. Schwartz LB, Bradford TR, Rouse C, Irani AM, Rasp G, Van der Zwan JK, Van del Linden PW Development of a new, more sensitive immunoassay for human tryptase use in systemic anaphylaxis. J Clin Immunol 1994 14 190-204. 

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. 

The cause of pruritus is unknown, although several mechanisms have been proposed. Vitamin A is known to accumulate in the skin and serum of patients with CKD, but a definite correlation with pruritus has not been established. Histamine may also play a role in the development of pruritus, which may be linked to mast cell proliferation in patients receiving hemodialysis. Hyperparathyroidism has also been suggested as a contributor to pruritus, despite the fact that serum PTH levels do not correlate with itching. Accumulation of divalent ions, specifically magnesium and aluminum, may also play a role in pruritus in patients with CKD. Other theories that have been proposed include inadequate dialysis, dry skin, peripheral neuropathy, and opiate accumulation.43... 

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