Allergic manifestations in women with silicone breast implants.

Introduction: Silicone breast implants (SBI) result in immune dysregulation and are associated with autoimmune diseases. Recently, we reported dysregulated levels of IgG autoantibodies directed against G protein-coupled receptors (GPCRs) of the autonomic nervous system which were linked to the autoimmune dysautonomia in silicone breast implant illness (SBII).

Aims: We aimed to explore the possible association between allergy with dysregulated IgE autoantibodies directed against GPCRs of the autonomic nervous system in women with SBI.

Tumor-Derived Extracellular Vesicles Induce CCL18 Production by Mast Cells: A Possible Link to Angiogenesis.

Mast cells (MCs) function as a component of the tumor microenvironment (TME) and have both pro- and anti-tumorigenic roles depending on the tumor type and its developmental stage. Several reports indicate the involvement of MCs in angiogenesis in the TME by releasing angiogenic mediators. Tumor cells and other cells in the TME may interact by releasing extracellular vesicles (EVs) that affect the cells in the region.

Extracellular Vesicles as Emerging Players in Intercellular Communication: Relevance in Mast Cell-Mediated Pathophysiology.

Mast cells are major effector cells in eliciting allergic responses. They also play a significant role in establishing innate and adaptive immune responses, as well as in modulating tumor growth. Mast cells can be activated upon engagement of the high-affinity receptor FcεRI with specific IgE to multivalent antigens or in response to several FcεRI-independent mechanisms.

Novel NCF2 Mutation Causing Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in the NADPH oxidase complex. Mutations in NCF2 encoding the cytosolic factor p67 result in autosomal recessive CGD. We describe three patients with a novel c.

Lung cancer-derived extracellular vesicles: a possible mediator of mast cell activation in the tumor microenvironment.

Activated mast cells are often found in the tumor microenvironment. They have both pro- and anti-tumorigenic roles, depending on the tumor type. Several lines of evidence suggest that the tumor microenvironment contains multiple soluble factors that can drive mast cell recruitment and activation.

MicroRNA Involvement in Allergic and Non-Allergic Mast Cell Activation.

Allergic inflammation is accompanied by the coordinated expression of numerous genes and proteins that initiate, sustain, and propagate immune responses and tissue remodeling. MicroRNAs (miRNAs) are a large class of small regulatory molecules that are able to control the translation of target mRNAs and consequently regulate various biological processes at the posttranscriptional level. MiRNA profiles have been identified in multiple allergic inflammatory diseases and in the tumor microenvironment.

Microvesicles derived from normal and multiple myeloma bone marrow mesenchymal stem cells differentially modulate myeloma cells' phenotype and translation initiation.

Multiple myeloma (MM) cells' interaction with the bone marrow (BM) microenvironment critically hinders disease therapy. Previously, we showed that MM co-culture with BM-mesenchymal stem cells (MSCs) caused co-modulation of translation initiation (TI) and cell phenotype and implicated secreted components, specifically microvesicles (MVs). Here, we studied the role of the BM-MSCs [normal donors (ND) and MM] secreted MVs in design of MM cells' phenotype, TI and signaling.

MicroRNA-4443 regulates mast cell activation by T cell-derived microvesicles.

Background: The mechanism by which mast cells (MCs) are activated in T cell-mediated inflammatory processes remains elusive. Recently, we have shown that microvesicles derived from activated T cells (mvT*s) can stimulate MCs to degranulate and release several cytokines.

Objective: The aim of this study was to characterize the contribution of microRNAs (miRs) delivered by microvesicles to MC activation.

The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation.

Background: It has recently been reported that mast cells (MC) can be activated to degranulate and release certain cytokines in response to direct physical contact with activated but not resting T cells or their membranes. The MAPK family members ERK and p38 were found to participate. In this work, we further characterize the signaling events involved in this novel pathway of activation.

T cell-derived microvesicles induce mast cell production of IL-24: relevance to inflammatory skin diseases.

Background: It has recently been shown that microvesicles derived from activated T cells can stimulate human mast cells (MCs) to degranulate and release several cytokines.

Objective: The aim of this study was to characterize microvesicle-induced MC expression patterns. Through identification of unique cytokine and chemokine expression, we attempted to reveal pathogenetic roles for this pathway of MC activation.

Immunotherapy with commercial venoms is efficacious for anaphylactic reactions to Vespa orientalis stings.

Background: Vespa orientalis (VO) stings occasionally induce anaphylaxis. In the absence of commercial VO venom, allergists use commercial venoms for immunotherapy, despite having no indication regarding efficacy. We attempted to examine the effectiveness of immunotherapy with commercial venoms in patients with VO allergy and to identify the venom accountable for this effect.

Mast cells as sources and targets of membrane vesicles.

In addition to being major effector cells in the elicitation of allergic responses, mast cells have been found to play a significant role in the establishment of innate and adaptive immune responses. This occurs, in part, by regulating the phenotype and function of immune cells such as T cells, B cells and dendritic cells, and by acting as antigen presenting cells. Indeed, mast cells have been found to be activated in various T cell-mediated inflammatory processes and to reside in close physical proximity to T cells.

Blood pressure modulation following activation of mast cells by cationic cell penetrating peptides.

Short cell penetrating peptides (CPP) are widely used in vitro to transduce agents into cells. But their systemic effect has not been yet studied in detail. We studied the systemic effect of the cell penetrating peptides, penetratin, transportan and pro-rich, on rat hemodynamic functions.

Mast cell activation by fibrinogen-related homologous c-terminal peptides (haptides) modulates systemic blood pressure.

Background: Haptides are a family of short peptides homologous to C-termini sequences of fibrinogen chains β and γ (haptides Cβ and preCγ, respectively) which were previously shown to penetrate and bind cells.

Objectives: This work investigates the systemic effect of the haptides with possible clinical implications.

Methods: Intra-arterial monitoring in rats recorded the haptides' effects on systemic blood pressure.

T cell-induced mast cell activation: a role for microparticles released from activated T cells.

Close physical proximity between mast cells and T cells has been demonstrated in several T cell-mediated inflammatory processes. However, the way by which mast cells are activated in these T cell-mediated immune responses has not been fully elucidated. We previously identified and characterized a novel mast cell activation pathway initiated by physical contact with activated T cells and showed that this pathway is associated with degranulation and cytokine release.

Characterization of ERK activation in human mast cells stimulated by contact with T cells.

Close physical proximity between mast cells and T cells has been demonstrated in several human conditions. We have identified and characterized a novel mast cell activation pathway initiated by contact with T cells, and showed that this pathway is associated with cytokine release. It has been shown recently that Ras is activated in this pathway.

Cognitive-performance recovery of Alzheimer's disease model mice by modulation of early soluble amyloidal assemblies.

A rationally designed oligomerization inhibitor interacts with early intermediate assemblies of amyloid-beta polypeptide (Abeta) through the aromatic elements and inhibits their assembly into the toxic oligomers that cause Alzheimer's disease by a unique C(alpha)-methylation beta-breakage strategy. The electrostatic potential of the low-energy conformation of the dipeptide inhibitor bound to Abeta is shown.

Inhibition of basic secretagogue-induced signaling in mast cells by cell permeable G alpha i-derived peptides.

Background: Basic secretagogues of connective tissue mast cells act as receptor mimetic agents that trigger mast cells by activating G proteins. This leads to simultaneous propagation of two signaling pathways: one that culminates in exocytosis, while the other involves protein tyrosine phosphorylation and leads to release of arachidonic acid metabolites. We have previously shown that introduction of a peptide that comprises the C-terminal end of G alpha i3 into permeabilized mast cells inhibits basic secretagogue-induced exocytosis [Aridor et al.

Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta regulate IgE receptor-triggered exocytosis in cultured mast cells.

We examined the possible occurrence and function of neuronal Ca(2+) sensor 1 (NCS-1/frequenin) in the mast cell line rat basophilic leukemia, RBL-2H3. This protein has been implicated in the control of neurosecretion from dense core granules in neuronal cells as well as in the control of constitutive secretory pathways in both yeast and mammalian cells. We show that RBL-2H3 cells, secretory cells of the immune system, endogenously express the 22-kDa NCS-1 protein as well as an immune-related 50-kDa protein.

Gi-mediated activation of the p42/p44 mitogen-activated protein kinases by receptor mimetic basic secretagogues is abrogated by inhibitors of endocytosis.

Exocytosis in mast cells, effector cells of allergic and inflammatory reactions, can be activated, in a receptor-independent manner, by a family of polycationic molecules (e.g. the Basic Secretagogues of mast cells) that activate directly heterotrimeric G-proteins that control exocytosis.