Cutaneous and systemic manifestations of mastocytosis. (1/170)

Mastocytosis is characterized by an excessive number of apparently normal mast cells in the skin and, occasionally, in other organs. Characteristic skin lesions, called urticaria pigmentosa, are present in most patients, but clinical presentation can vary from a pruritic rash to unexplained collapse and sudden death. These lesions are typically tan to red-brown macules that appear on the trunk and spread symmetrically. Patients with mastocytosis often have a long history of chronic and acute symptoms that were unrecognized as mastocytosis. Skin lesions may or may not accompany systemic mastocytosis. Systemic disease may involve the gastrointestinal tract, the bone marrow or other organs. Even when the disease is considered as a possibility by the physician, the diagnosis can be difficult because of special technical requirements necessary for biopsy and because of the problems with biochemical testing. Drug therapy is initiated to stabilize mast cell membranes, to reduce the severity of the attacks and to block the action of inflammatory mediators. The mainstay of therapy is histamine H1 and H2 blockers and the avoidance of triggering factors.  (+info)

Stem cell factor is localized in, released from, and cleaved by human mast cells. (2/170)

Stem cell factor (SCF) is the most important cytokine regulating human mast cell growth and functions. The immunogold technique showed SCF in the secretory granules of skin mast cells and in lung parenchymal mast cells (HLMC). Immunoreactive SCF (iSCF) was detected in cell lysates of HLMC, but not in basophils; iSCF and histamine were detected in supernatants of HLMC 3 min after challenge with anti-FcepsilonRI or anti-IgE, and iSCF in supernatants rapidly declined after 30 min, whereas histamine remained unchanged for 120 min. HPLC and electrospray mass spectrometry (ES/MS) analysis of recombinant human SCF1-166 (18,656. 9 +/- 0.9 Da) treated with chymase showed a polypeptide of 17,977.1 +/- 0.6 Da and a minor component of 697.4 +/- 0.1 Da generated by specific cleavage at Phe159. SCF1-166 and SCF1-159 similarly activated HLMC, potentiated anti-IgE-induced activation of these cells, and stimulated HLMC chemotaxis. SCF159-166 had no effect on mast cells. Western blot analysis of supernatants of anti-IgE-activated HLMC incubated with recombinant human SCF1-166 showed that SCF1-166 was rapidly cleaved to SCF1-159 and SCF1-144. Experiments with supernatants of anti-IgE-activated HLMC incubated with SCF1-166 yielded similar results. In conclusion, SCF is stored in mast cell secretory granules and is immunologically released by human mast cells. SCF1-166 is rapidly and specifically cleaved to SCF1-159 by chymase, which retains its biological effect on mast cells. SCF is also cleaved by other proteases to several SCF species whose possible biological activities remain to be established.  (+info)

An unusual presentation of systemic mastocytosis. (3/170)

A 47 year old man presented with mastocytosis, a disease process characterised by proliferation of mast cells. The clinical features and outcome are discussed.  (+info)

Cutaneous mucinosis and mastocytosis in a shar-pei. (4/170)

A 7-year-old shar-pei was presented because of a recurrent dermatologic condition. Skin biopsies revealed an idiopathic (primary) cutaneous mucinosis that initially responded to corticosteroids. The condition reappeared 2 years later and subsequent biopsies revealed a mast cell tumor in some of the skin sites previously diagnosed with mucinosis.  (+info)

c-Kit and c-kit mutations in mastocytosis and other hematological diseases. (5/170)

Mast cells (MC) are tissue elements derived from hematopoietic stem cells. Their differentiation and proliferation processes are under the influence of cytokines, including one of utmost importance known as stem cell factor (SCF). SCF receptor is encoded by the protooncogene c-kit, belongs to the type III receptor tyrosine kinase subfamily, and is also expressed on other hematopoietic or non-hematopoietic cells. Ligation of c-kit receptor by SCF induces its dimerization, followed by induction of multiple intracellular signaling pathways leading to cell proliferation and activation. Mastocytosis, a relatively rare group of diseases characterized by accumulation of MC in various tissues, are found isolated or sometimes associated with other hematological malignancies in humans. Although the initial events leading to mastocytosis are not yet unraveled, alterations of the c-kit gene have been described. Particularly interesting are acquired mutations resulting in a constitutively activated receptor, possibly involved in the increased numbers of MC in tissues. For this reason, future strategies might be envisaged to target specifically the mutated c-kit and/or its intracellular signaling.  (+info)

A role of mast cell glycosaminoglycans for the immunological expulsion of intestinal nematode, Strongyloides venezuelensis. (6/170)

We examined effects of mast cell glycosaminoglycans on the establishment of the intestinal nematode, Strongyloides venezuelensis, in the mouse small intestine. When intestinal mastocytosis occurred, surgically implanted adult worms could not invade and establish in the intestinal mucosa. In mast cell-deficient W/Wv mice, inhibition of adult worm invasion was not evident as compared with littermate +/+ control mice. Mucosal mastocytosis and inhibition of S. venezuelensis adult worm mucosal invasion was tightly correlated. To determine effector molecules for the invasion inhibition, adult worms were implanted with various sulfated carbohydrates including mast cell glycosaminoglycans. Among sulfated carbohydrates tested, chondroitin sulfate (ChS)-A, ChS-E, heparin, and dextran sulfate inhibited invasion of adult worms into intestinal mucosa in vivo. No significant inhibition was observed with ChS-C, desulfated chondroitin, and dextran. ChS-E, heparin, and dextran sulfate inhibited adhesion of S. venezuelensis adult worms to plastic surfaces in vitro. Furthermore, binding of intestinal epithelial cells to adhesion substances of S. venezuelensis, which have been implicated in mucosal invasion, was inhibited by ChS-E, heparin, and dextran sulfate. Because adult worms of S. venezuelensis were actively moving in the intestinal mucosa, probably exiting and reentering during infection, the possible expulsion mechanism for S. venezuelensis is inhibition by mast cell glycosaminoglycans of attachment and subsequent invasion of adult worms into intestinal epithelium.  (+info)

Nitric oxide mediates intestinal pathology but not immune expulsion during Trichinella spiralis infection in mice. (7/170)

The relationship between intestinal pathology and immune expulsion of gastrointestinal (GI) nematodes remains controversial. Although immune expulsion of GI helminth parasites is usually associated with Th2 responses, the effector mechanisms directly responsible for parasite loss have not been identified. We have previously shown that while the intestinal pathology accompanying the expulsion of the GI parasite Trichinella spiralis may be dependent on IL-4 and mediated by TNF, parasite loss is independent of TNF. In contrast, intestinal pathology in other disease models has been attributed to Th1 cytokines, although it closely resembles that seen in helminth infections. Whereas production of inducible NO synthase (iNOS) in the gut is important for both homeostasis of the epithelial layer and in protection against pathogenic microorganisms, overproduction of NO has been implicated in the pathogenesis of a number of inflammatory conditions. We therefore investigated the role of NO in T. spiralis infection using iNOS-deficient mice. iNOS-/- and iNOS-/+ mice were infected with T. spiralis, and parasite expulsion and intestinal pathology were followed. Parasite expulsion proceeded similarly in both groups of animals, but significant intestinal pathology was only observed in the heterozygous mice. Thus it appears that, although the protective effects of Th2 responses in GI helminth infection do not require NO, this mediator contributes substantially to the associated enteropathy. NO may therefore be an important mediator of enteropathy in both Th1- and Th2-inducing conditions.  (+info)

Pulmonary manifestation of systemic mast cell disease. (8/170)

Systemic mast cell disease is a rare disease of unknown aetiology. Systemic infiltration and proliferation of mast cells in skin, bone marrow, gastrointestinum and lymph nodes is the central pathological feature. This study reports a patient with mastocytosis of the skin (urticaria pigmentosa) for 10 yrs. The patient was referred to hospital for dyspnoea. Chest radiograph showed moderate reticular infiltration of both lungs, computerized tomography revealed multiple lymph nodes of the mediastinum and faint nodular lesions of middle and upper areas of lungs. Transbronchial biopsy demonstrated mast cell infiltration of the lung with formation of mast cell granuloma. According to the current literature, systemic mast cell disease with pulmonary involvement is a very rare entity. After a treatment with interferon alpha-2a over 6 months, the patient's condition and particularly dyspnoea showed improvement in parallel with an amelioration of the lesions as demonstrated by thorax computed tomography.  (+info)