Nataliya M Kushnir-Sukhov's research while affiliated with National Institute of Allergy and Infectious Diseases and other places

Publications (13)

Article
Mast cells (MCs) have a central role in the induction of allergic inflammation, such as seen in asthma, and contribute to the severity of certain autoimmune diseases, such as rheumatoid arthritis. The MC thus represents an important inflammatory cell, and one which has resisted therapeutic attempts to alter its role in disease. Because bone marrow-...
Article
Mastocytosis is characterized by the abnormal growth and accumulation of mast cells in one or more organ systems and may vary significantly in clinical presentation and severity. The disease is unusual, is known to affect both males and females in all age groups, and in most cases is not inherited. While knowledge of mast cell growth and differenti...
Article
Mastocytosis is a clonal disorder associated with an increased mast cell burden. We have recently demonstrated the ability of human mast cells to express and be activated through multiple serotonin receptors; to synthesize and release serotonin; and that mastocytosis patients may have abnormal serotonin levels. As serotonin has been implicated in t...
Article
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Idiopathic anaphylaxis remains a perplexing disorder in which existing prophylactic therapy is inadequate. In this prospective study, we sought to determine whether patients with idiopathic anaphylaxis might have evidence for a clonal disorder of mast cells related to mastocytosis and for which novel targeted therapies might be considered. We repor...
Article
Full-text available
Ionizing gamma radiation has several therapeutic indications including bone marrow transplantation and tumor ablation. Among immune cells, susceptibility of lymphocytes to gamma radiation is well known. However, there is little information on the effects of gamma radiation on mast cells, which are important in both innate and acquired immunity. Pre...
Article
Full-text available
Inhalation of crystalline silica results in pulmonary fibrosis and silicosis. It has been suggested that mast cells play a role in these conditions. How mast cells would influence pathology is unknown. We thus explored mast cell interactions with silica in vitro and in B6.Cg-kit(W-sh) mast cell-deficient mice. B6.Cg-kit(W-sh) mice did not develop i...
Article
The neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) is implicated in enhancing inflammatory reactions of skin, lung, and gastrointestinal tract. To determine whether 5-HT acts, in part, through mast cells (MC), we first established that mouse bone marrow-derived MC (mBMMC) and human CD34(+)-derived MC (huMC) expressed mRNA for multiple 5-HT...
Article
Mastocytosis is associated with a pathological increase in tissue mast cells. Associated skeletal problems include a decrease in bone density and pathological fractures. In order to explore the relationship between bone density and the severity of mastocytosis, 21 patients with mastocytosis who underwent dual-energy X-ray absorptiometry were entere...

Citations

... However, the heterogeneity of mast cells lies also in their ontogeny, and likely arises from their origins during early development or adulthood as well as the stimuli they receive, potentially in ways that are not yet fully characterized. Some mast cells, although not their precursors, are radioresistant and long-lived, possibly surviving for years in certain tissues 23 . In addition, they have dynamic responses to infections and inflammatory stimuli, being capable of local proliferation in some circumstances as well as survival and regranulation following activation, which contrasts with the propensity of many immune cells to undergo apoptosis after activation. ...
... According to Soule et al, MCs are resistant to cytotoxicity after radiation, and radiation has no effect on Kit and FceRI receptor expression. MCs degranulation is inhibited transiently and recovers within 24 hours after irradiation in human MCs, and MCs remain responsive to TLR-mediated signalling and produce cytokines (38). Westbury et al. observed a post-irradiation increase in the number of MCs (39). ...
... 210 MSCs alleviate allergic inflammation by suppressing degranulation and pro-inflammatory factors production in mast cells in a COX2-dependent manner. 211 Importantly, PGE 2 preserves the immune privilege of allogeneic MSCs during therapeutic infusion. 212 MSCs-derived PGE 2 induces CD4 + T cell differentiation into Tregs along with TGFβ1, by means of direct cell-cell contact. ...
... The mast cell produces and secretes heparin and various enzymes that affect blood clotting and blood vessels. Interestingly for us, this cell also contains serotonin (Kushnir-Sukhov et al., 2008). E represents another form of so-called paracrine signaling. ...
... In these patients a higher bone turnover has been found in both osteoporosis and osteosclerosis [68]; therefore, fractures can be associated with both of these disorders. In addition, the level of tryptase may predict mast cell mass and simultaneously best correlate to higher bone density; however, this high bone density does not protect against fracture in SM patients [69]. ...
... To assess this, we examined in vitro activation of mast cells by NM, and used both wild type and mast cell deficient mice to examine the lung inflammation following NM exposure. The B6.Cg-KitW-sh/HNihrJaeBsm (Kit W-sh ; mast cell deficient) mice have a transversion mutation on the c-KIT receptor, necessary for the proliferation and maturation of mast cells and have been used extensively to define the role of mast cells in various diseases (Brown et al., 2007;Grimbaldeston et al., 2005). These studies explored the novel concept that mast cells play a critical role in pulmonary inflammation following SM exposure and may provide a novel therapeutic target in SM toxicity. ...
... Most immune cells express 5-HT receptors. 5-HT1 is mainly expressed in innate immune cells such as the mast cells (Kushnir-Sukhov et al., 2006), macrophages (Nakamura et al., 2008), DCs (Durk et al., 2005), and monocytes (Soga et al., 2007); 5HT-2 is expressed in eosinophils and macrophages (Mikulski et al., 2010). In the adaptive immune system, proliferated T cells mainly express 5-HT1B, 5-HT2A, and 5-HT7, and B cells mainly express 5-HT1A and 5-HT3 (Yin et al., 2006;Inoue et al., 2011). ...
... Mast cell mediators involved in inflammation include proteases, cytokines (some of which are prestored), eicosanoids (such as leukotrienes and prostaglandins) and even some neurotransmitters (such as serotonin) 80,81 . There are numerous ways in which mast cells can induce and sustain inflammation in tissues, including by promoting the recruitment of neutrophils, eosinophils and T cells that can help to clear an infection 18 . ...
... Bone marrow mastocytosis (BMM) is a provisional WHO variant of ISM that fulfills the criteria of SM and shows the involvement of the bone marrow (BM) but the absence of skin lesions [2,9,10]. A number of recent studies have shown that patients with BMM frequently suffer from severe anaphylaxis due to an IgE-mediated allergy to bee or wasp venom and sometimes also from unexplained (idiopathic) anaphylaxis [11][12][13][14][15][16]. In addition, BMM patients may suffer from osteoporosis [17,18]. ...