Mast cells, characterization

M, Marone G Human heart mast cells. Isolation, purification, ultrastructure and immunologic characterization. J Immunol 1995 154 2855. 28... 

Mastocytosis is a disorder characterized by increased numbers of mast cells in the skin, bone marrow, gastrointestinal tract, Uver, spleen, and lymph nodes [9,10]. The prevalence is unknown the incidence has been roughly estimated to be 3-7 new patients per million per year [9]. Most cases are sporadic with only a limited number (50-100) of cases with mastocytosis reported to pass from generation to generation [11], Mastocytosis presents at any age, although most cases occur during the first 2 years of life (childhood-onset) or after puberty (adult-onset) [9]. Mastocytosis in childhood often is self-limited and involves only the skin, whereas the course in patients with adult-onset disease is normally chronic and includes systemic involvement. 

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]. 

Escribano L. Orfao A, Diaz-Agustin B, et al Indolent systemic mast cell disease in adults immunopheno-typic characterization of bone marrow mast cells 46 and its diagnostic implications. Blood 1998 91 2731 -2736. 

Mast cell protease A3 is less well characterized than tryptase and chymase in terms of physiological substrates. It is involved, among its other functions, in angiotensin metabolism. 

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. 

As observed by Celus, a Roman physician during the first century A.D., the four cardinal signs characterize inflammation swelling, redness, heat, and pain. Swelling/edema occurs in response to the accumulation of fluids from damaged capillaries following injury. Increased fluid accumulation leads to increase capillary permeability. Histamine, produced and released by resident mast cells, also... 

The involvement of mast cells in host protection against nematode infection is well characterized in T. spiralis infection. W/Wv mice exhibited a significant delay in worm expulsion, and treatment with either anti-SCF or anti-SCF receptor monoclonal antibody dramatically inhibited mast cell responses and expulsion of T. spiralis for the duration of treatment (Donaldson et al., 1996). W/Wv mice also lack interstitial cells of cajal and intraepithelial y T cells (Maeda et al., 1992 Puddington et al., 1994), which may contribute to the impaired response in these animals (see below). However, supporting evidence of a role for mast cells in protection against T. spiralis comes from studies in which overexpression of IL-9 in mice (which is known to influence the mast cell responses see above) resulted in an extremely rapid mast cell-dependent expulsion of T. spiralis (Faulkner et al., 1997). 

Hough, L.B., Goldschmidt, R. C., Glick, S. D. and Padawer, J. Mast cells in rat brain characterization, localization, and histamine content. In C. R. Ganellin and J. C. Schwartz (eds), Frontiers in Histamine Research A Tribute to Heinz Schild. Advances in the biosciences. New York Pergamon Press, 1985, pp. 131-140. 

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. 

Several other cell types have also been shown to secrete histamine-releasing activity, some of which may be peptide in nature (although more work is necessary for a definitive characterization). For example, human lung macrophages cultured for 24 h have been shown to release a soluble factor (12 and 30 kDa) that stimulates isolated human lung mast cells and human basophils to release histamine [ 145]. The generation and release of this factor developed over time (> 1 h) and was blocked by cycloheximide, indicating that protein... 

Several other factors - some IgE-dependent, others IgE-independent - have been reported to modulate histamine release from basophils and mast cells [ 149, 150], Elowever, these factors, which are produced by mononuclear cells, have not been chemically characterized or well defined. 

Slender spindle-shaped fibroblasts are the commonest cell to be found in connective tissue. These cells, which manufacture matrix collagen and proteoglycans, have an elliptical nucleus and a cytoplasm which is contains extensive rough endoplasmic reticulum and Golgi apparatus, which are typical features of secretory cells. Mast cells are found widely within connective tissues and like fibroblasts these are secretory cells and characterized by a very granular cytoplasm. Almost as numerous as the fibroblasts and cytologically very similar to them, are macrophages, also called histiocytes or littoral cells. 

SCF is encoded by the mouse Steel (SI) loci (Zsebo et al, 1990). The Sl-Dickie allele of mutant mice (Sf ) encodes a smaller protein due to deletions of the transmembrane and intracellular domains. SI cells exclusively express a secreted form of SCF (Flanagan et al, 1991). Another mutation of the Steel locus, Sl/Sl, results in complete loss of SCF production (Zsebo et al, 1990). Mutations of both the Steel and SI loci result in similar phenotypic disorders of hematopoiesis characterized by reduction in stem cell numbers, anemia, mast cell- and repair deficiencies (Nocka et al., 1989 McCulloch et al., 1965). Phenotypes of Sf mice show that the membrane inserted SCF must have an... 

Feoktistov I, Biaggioni I (1998) Pharmacological characterization of adenosine A2B receptors studies in human mast cells coexpressing A2A and A2B adenosine receptor subtypes. Biochem Pharmacol 55(5) 627-633... 

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