Mast cells proliferation

Zsebo KM, Metcalfe DD. Geissler EN. Galli SJ Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem dS cell factor. Proc Natl Acad Sci USA 1991 88 6382. 

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]. 

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... 

Growth of multi-potential stem cells, myeloid, erythroid, mast cells Increases MHC Class II expression on macrophages, promotes mast cell proliferation, promotes hematopoietic precursors, isotype switching in IgGl and IgE, T cell proliferation, activation of B cells from resting state, increased MHC Class II expression, proliferation in presence of Ag, increased IL-2R receptor expression... 

Pruritus 5 Inadequate dialysis Skin dryness Secondary hyperparathyroidism Abnormal skin levels of electrolytes Histamine release Mast cell proliferation... 

M28. Matsumoto, M., Ichimaru, K., and Horie, A., Pruritus and mast cell proliferation of the skin in end-stage renal failure. Clin. Nephrol. 23, 285-288 (1985). 

GM-CSF acts on virtually the same set of cells as IL-3, but is unable to stimulate mast cell proliferation. In addition to T cells, endothelial cells and fibroblasts are also important sources of GM-CSF (G23). GM-CSF is a 127-amino-acid molecule... 

Kempna, P, Reiter, E, Arock, M., Azzi, A., and Zingg, J.M., Inhibition of HMC-1 mast cell proliferation by vitamin E involvement of the protein kinase B pathway, J. Biol. Chem. 279 (49), 50700-50709, 2004. 

SCF (recombinant product ancestim) is an early-acting hematopoietic growth factor that stimulates the proliferation of primitive hematopoietic and nonhema-topoietic cells [7]. In vitro, SCF has minimal effect on hematopoietic and nonhematopoietic progenitor cells, but it synergistically increases the activity of other hematopoietic growth factors, such as G-CSF, GM-CSF, and EPO. SCF stimulates the generation of dendritic cells in vitro and mast cells in vivo. 

Although mast cells and basophils probably account for >90% of stored histamine in the body, histamine is also present in platelets, enterochromaffin-like cells, endothelial cells, and neurons. Histamine can act as a neurotransmitter in the brain. Histaminergic nerves have their cell bodies within a very small area of the brain (the magnocellular nuclei of the posterior hypothalamus) but have axons in most areas of the forebrain. There is also evidence for axons projecting into the spinal (Fig. 1) cord. Finally, there is evidence that histamine synthesis can be induced in tissues undergoing rapid tissue growth and repair. In certain neonatal tissues (e.g. liver), the rate of synthesis of this unstored diffusable histamine (termed nascent histamine) is profound and may point to a role for histamine is cell proliferation. 

In spite of the above-mentioned similarities between basophils and mast cells, they differ in many other aspects [1,2]. Basophils complete their differentiation within the bone marrow, and mature basophils circulate in the peripheral blood and do not usually infiltrate into peripheral tissues unless inflammation takes place. Mast cells originate from hematopoietic cells in the bone marrow as do basophils, but they mature in peripheral tissues after their bone marrow-derived precursors enter the circulation and migrate into peripheral tissues. Mature mast cells reside in peripheral tissues and do not usually circulate in the peripheral blood. The lifespan of basophils is very short (several days), in contrast to that of mast cells (weeks to months). Basophils do not proliferate once they terminally differentiate whereas mature mast cells keep potential to expand in response to various stimuli. These differences between basophils and mast cells, including distinct anatomical localization, suggest their differential roles in vivo. 

Theophylline appears to produce bronchodilation by inhibiting phosphodiesterases, which may also result in antiinflammatory and other nonbronchodilator activity through decreased mast cell mediator release, decreased eosinophil basic protein release, decreased T-lymphocyte proliferation, decreased T-cell cytokine release, and decreased plasma exudation. 

Substance P, calcitonin-gene-related peptide (CGRP), and neurokinin A have been identified by immunocytochemistry in primary sensory neurones and in cutaneous sensory nerve terminals and these are often in close proximity to mast cells [54, 56], For example, in Lewis rats that were infected with the parasitic larvae of Nippostrongylis brasiliensis in order to induce a proliferation of mucosal mast cells, nearly two-thirds of the lamina propria mast cells were in intimate contact with peptidergic nerves containing SP and CGRP, while an additional 20% of the mast cells were within 2 gm [54], All three peptides are... 

Recently, NGF has been shown to cause a significant proliferation of connective tissue mast cells when injected subcutaneously into newborn (day 1) rats [122]. This effect of NGF is blocked by DSCG, which suggests that products released from NGF-stimulated mast cells are responsible (directly or indirectly) for the proliferation or recruitment of other mast cells. In adult rats, a similar proliferation of mucosal mast cells in the small intestine is known to accompany an infection by intestinal nematode, N. brasilensis [123] and has also been reported to accompany the repeated injections of compound 48/80 [ 124], It may be relevant in this regard that mast cells are frequently prominent in a wide variety of fibrotic conditions such as neurofibromatosis where itching around the growing neurofibroma is a common symptom [125]. Treatment of neurofibromatosis with ketotifen, a mast cell stabilizer similar to DSCG, results... 

Lymphocyte-activating factor enhances activation of T and B cells, NK cells, and macrophages T-cell growth factor stimulates T-cell growth and effector differentiation stimulates B-cell proliferation/differentiation Mast-cell growth factor stimulates... 

IL-3 also has effects on mature cells. Those reported include the enhancement of the cytotoxicity of macrophages, stimulation of the proliferation of tissue-derived mast cells and (in the presence of endotoxin) the stimulation of the tumouricidal activity of monocytes, possibly via enhanced production of tumour necrosis factor (TNF). However, there are no reported effects of IL-3 on mature neutrophil function. 

The interaction of antibody-antigen complexes with cells of the immune system results in the activation of a variety of responses ranging from ADCC, mast-cell degranulation, lymphocyte proliferation, antibody secretion and phagocytosis. All these processes are activated via the binding of the Fc domain of the antibody molecule, which is exposed during antibody-... 

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