The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase. Limited treatment options exist for aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL). We evaluated whether PKC412, a small-molecule inhibitor of KIT with a different chemical structure from imatinib, may have therapeutic use i...

In vitro culture systems using bone marrow cells from BALB/C mice were set up in medium supplemented with spleen-derived medium. Bone marrow cells grown in spleen-derived medium gave rise to cultures containing >97% mast cells. The cells were used in polarisation chemotaxis assays with the intention of determining the effect of nerve tissue-derived neurotransmitters on mast cell migration. ...

Kit is a receptor-type tyrosine kinase found on the plasma membrane. It can transform mast cells through activating mutations. Here, we show that a mutant Kit from neoplastic mast cells from mice, Kit(D814Y), is permanently active and allows cells to proliferate autonomously. It does so by activating two signalling pathways from different intracellular compartments. Mutant Kit from the cell sur...

IgE-dependent activation of mast cell activation is often associated with symptoms attributed to activation of sensory nerves. Depending on the tissues involved such symptoms include itching, sneezing, irritation, vasodilation, and reflex secretions. In the present study, we hypothesize that sensory neuroactive mediators released from mast cells may include agonists of recently discovered orpha...

Connective tissue mast cells (CTMC) reside near to blood vessels in connective tissues and are found also in the peritoneal cavity in many species (1) . Once thought to be terminally differentiated cells, CTMC arenowknown to proliferate in response to activated spleen cell-conditioned medium (SCCM) or to a mixture of IL-3 and IL-4 (2, 3) . CTMC, which contain large quantities of heparin and his...

Mast cells possess specialized granules that, upon stimulation of surface FcR with IgE, fuse with the plasma membrane, thereby releasing inflammatory mediators. A family of membrane fusion proteins called SNAREs, which are present on both the granule and the plasma membrane, plays a role in the fusion of these granules with the plasma membrane of mast cells. In addition to the SNAREs themselves...

Mast cells have the ability to react to multiple stimuli, implicating these cells in many immune responses. Specific signals from the microenvironment in which mast cells reside can activate different molecular events that govern distinct mast cells responses. We previously demonstrated that hydrogen peroxide (H(2)O(2)) promotes IL-4 and IL-6 mRNA production and potentates FcepsilonRI-induced c...

Mastocytosis is a clonal proliferation of mast cells that accumulates in one or more organs [1]. This disorder is heterogenous, ranging from skin lesion that may spontaneously regress to multiple organ lesions that show a highly aggressive course, and a recent World Health Organization Classification divides it into 7 subtypes: cutaneous mastocytosis, indolent systemic mastocytosis, systemic ma...

Communication between nerves and mast cells is a prototypic demonstration of neuroimmune interaction. However, whether mast cell activation occurs as a direct response to neuronal activation or requires an intermediary cell is unclear. Addressing this issue, we used an in vitro coculture approach comprising cultured murine superior cervical ganglia and rat leukemia basophilic cells (RBLs; posse...

Diagnosis of systemic mastocytosis (SM) is mainly based on the morphological demonstration of compact mast cell infiltrates in various tissue sites. In almost all patients such infiltrates are detected in the bone marrow. Reliable immunohistochemical markers for the diagnosis and grading of SM have been established, but various differential diagnoses including myeloproliferative neoplasms, baso...