Combinatorial Genomic Biomarkers Associated with High Response in IgE-Dependent Degranulation in Human Mast Cells.

Mast cells are the major effector cells that mediate IgE-dependent allergic reactions. We sought to use integrated network analysis to identify genomic biomarkers associated with high response in IgE-mediated activation of primary human mast cells. Primary human mast cell cultures derived from 262 normal donors were categorized into High, Average and Low responder groups according to their activation response profiles.

Human mast cells induce osteoclastogenesis through cell surface RANKL.

Objectives: We employed the co-culture of CD34 stem cell-derived human mast cells (HMC) and human monocyte-derived osteoclast precursors to evaluate if mast cells contribute to the pathogenesis of osteoporosis through regulation of osteoclast proliferation and activation.

Methods: Mature HMC and osteoclast precursors were cultured from monocytes isolated from human buffy coat. The osteoclast precursors were incubated with HMC or receptor activator of nuclear factor kappa-B ligand (RANKL) for a week prior to determination of osteoclast maturation through characterization by their morphology and tartrate resistant acid phosphatase (TRAP) expression.

6-O-angeloylplenolin inhibits anti-IgE-stimulated human mast cell activation via suppressing calcium influx and ERK phosphorylation.

Objectives: Mast cells are important immune cells that primarily localize in the interface between the host and external environment, and protect us from pathogen infection. However, they are also involved in the pathology of allergic diseases such as asthma and atopic dermatitis. A novel S phase kinase-associated protein 1 (SKP1) inhibitor 6-O-angeloylplenolin (6-OAP), was studied with its potential ability to alleviate the anti-IgE-induced inflammatory responses of primary human cultured mast cells (HCMCs) and LAD2 cell line.

Degradation of Monocyte Chemoattractant Protein-1 by Tryptase Co-Released in Immunoglobulin E-Dependent Activation of Primary Human Cultured Mast Cells.

Background: Mast cells are key immune effector cells which release chemokines, proteases, and other inflammatory mediators upon activation by immunological stimuli. The aim of this study was to investigate the effects of co-releasing proteases on the kinetics of release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in immunoglobulin E (IgE)-mediated activation of human mast cells.

Methods: Homogenous populations of mature and functional primary human mast cells were generated from CD34+ progenitors originated from buffy coats of healthy adult donors.

Immobilized Osteopontin Enhances Adhesion but Suppresses Cytokine Release of Anti-IgE Activated Human Mast Cells.

Osteopontin (OPN) is an Arg-Gly-Asp (RGD)-containing extracellular matrix protein which is upregulated in inflamed tissues and has been reported to modulate mast cell activities in mice. Due to the known heterogeneity among mast cells of different species and the important roles of mast cells in allergic reactions, we investigated the effects of human OPN (hOPN) on human mast cell activities. Mature primary human cultured mast cells (HCMC) were derived from peripheral blood CD34 progenitors and the modulation of their activation by soluble and plate-bound immobilized hOPN were examined by studying their release of inflammatory mediators (histamine, IL-5, IL-8, TNF-α, and VEGF) and matrix adhesion following stimulation by anti-IgE.

Author Correction: Novel six-week protocol for generating functional human connective tissue-type (MC) mast cells from buffy coats.

The online version of the original article can.

Novel six-week protocol for generating functional human connective tissue-type (MC) mast cells from buffy coats.

Objective: The aim of this study was to develop a novel protocol for generating large populations of fully mature and functional human mast cells (HMC) from CD34 hematopoietic stem cells which require less culturing time than previously reported methods.

Methods: CD34 cells isolated from fresh human buffy coats were sequentially cultured with different combinations of SCF, IL-6, IL-3, IL-9 and IL-4 under selected culturing conditions and time periods. Cells were then harvested for immunohistochemical characterization of morphological phenotypes and were functionally characterized by assessing their responses to IgE-dependent and -independent stimuli by measuring the release of inflammatory mediators and cytokines.

Impaired Toll-like receptor 2-mediated Th1 and Th17/22 cytokines secretion in human peripheral blood mononuclear cells from patients with atopic dermatitis.

Background: Impaired Toll-like receptor 2 (TLR2) function has been associated with the pathogenesis of atopic dermatitis (AD). However, there are only few studies reporting on the TLR2-induced immunological responses of circulating leucocytes of AD patients. We thus investigated the expression and secretion of Th1, Th2 and Th17/22 cytokines triggered by TLR2 ligands in human peripheral blood mononuclear cells (PBMCs) from AD patients.

Differential effects of the Toll-like receptor 2 agonists, PGN and Pam3CSK4 on anti-IgE induced human mast cell activation.

Mast cells are pivotal in the pathogenesis of allergy and inflammation. In addition to the classical IgE-dependent mechanism involving crosslinking of the high-affinity receptor for IgE (FcεRI), mast cells are also activated by Toll-like receptors (TLRs) which are at the center of innate immunity. In this study, we demonstrated that the response of LAD2 cells (a human mast cell line) to anti-IgE was altered in the presence of the TLR2 agonists peptidoglycan (PGN) and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4).

Suppression of mast cell activity contributes to the osteoprotective effect of an herbal formula containing Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae.

Objectives: Mast cells are believed to contribute to the pathogenesis of osteoporosis as their number is increased in osteoporotic bones. Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae are three Chinese herbs traditionally for tonifying the 'kidney system' and a herbal formula (ELP) containing the respective herbs at the weight ratio of 5 : 4 : 1 was shown to prevent osteoporosis. This study evaluated if suppression of mast cell accumulation and activity contribute to the anti-osteoporotic action of ELP.

Cyclic guanosine monophosphate dependent pathway contributes to human mast cell inhibitory actions of the nitric oxide donor, diethylamine NONOate.

We have previously demonstrated that exogenous nitric oxide (NO) inhibited anti-IgE-mediated histamine release from human cultured mast cells. In the current study, we further investigated if syntheses of eicosanoids and cytokines were also suppressed by NO donors and evaluated if activation of soluble guanylyl cyclase (sGC) was an underlying mechanism. The effects of the NO donor diethylamine NONOate (DEA/NO) on IgE-dependent syntheses of eicosanoids (prostaglandin D(2) and cysteinyl leukotrienes) and cytokines (tumor necrosis factor-alpha and interleukin-8) from buffy coat derived human cultured mast cells were examined.

Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses inflammatory mediators release from mast cells.

Background: PentaHerbs formula (PHF) containing Cortex Moutan, root bark of Paeonia suffruticosa Andr. (Ranunculaceae), Cortex Phellodendri, bark of Phellodendron chinensis Schneid. (Rutaceae), Flos Lonicerae, flower of Lonicera japonica Thunb.

Induction of nitric oxide synthases in primary human cultured mast cells by IgE and proinflammatory cytokines.

The mast cells have been suggested to be a cellular source of nitric oxide (NO) which level is increased in the pathogenesis of asthma. However, isoforms of the NO generating enzyme, nitric oxide synthase (NOS), in primary human mast cells have not been defined due to the lack of a suitable model. We hence examined directly the expression of NOS mRNA and proteins in primary human cultured mast cells (HCMC).

Histamine release from human buffy coat-derived mast cells.

Mast cells are unique immune cells that release a spectrum of chemical mediators contributing to the inflammatory symptoms of allergic disorders. Although mast cell biology has been extensively studied in the rodents, research on human mast cells is hampered by the lack of a convenient preparation source. This problem has now been addressed by culturing human mast cells from CD34(+) progenitors.

Functional characterization of human mast cells cultured from adult peripheral blood.

Mast cells are important effector cells of allergy and techniques for culturing human mast cells have been developed in recent years. In the current investigation, we studied the phenotypic and functional characteristics of mast cells cultured from adult human peripheral blood mononuclear cells. Mature human mast cells were obtained by first culturing mononuclear cells in methylcellulose containing stem cell factor (SCF), IL-3 and IL-6 for six weeks and subsequently in liquid medium containing SCF and IL-6 for another six weeks.