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Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells

Department of Dermatology, University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Yamanashi, Japan.
European Journal of Immunology (Impact Factor: 4.52). 02/2008; 38(2):489-99. DOI: 10.1002/eji.200737057
Source: PubMed

ABSTRACT Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and FcϵRI aggregation in bone marrow-derived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN–/–) and -sufficient (OPN+/+) mice without significant differences in yield, purity, granularity, and viability. Using OPN–/– FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin αv). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN–/– mice compared with OPN+/+ mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions.
See accompanying commentary at http://dx.doi.org/10.1002/eji200738131

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Available from: Hironori Matsushima, Jul 12, 2014
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    • "Osteopontin (OPN), also released by mast cells, functions in the balance and maintenance of mineralization, thus contributing to the control of bone metabolism (Chiappetta and Gruber 2006; Bulfone-Paus and Paus 2008). OPN was found to stimulate degranulation and migration of mast cells in vitro and OPN (-/-) mice displayed reduced IgE-mediated passive cutaneous anaphylaxis (Nagasaka et al. 2008). "
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    ABSTRACT: Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 07/2014; 62(10). DOI:10.1369/0022155414545334 · 1.22 Impact Factor
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    • "On the other hand, the involvement of OPN in the Th2-associated allergic responses was extensively investigated and revealed that OPN may be implicated in the development of lower airway allergic inflammatory diseases, such as asthma [7, 8]. It is also observed that OPN could augment both IgE-mediated mast cell degranulation and mast cell chemotaxis in vitro [9]. Furthermore, OPN is reported to be able to suppress antigen-specific production of IL-13, which is responsible for the enhancement of both proinflammatory cytokine production from macrophages and IgE production, when CD4+ T cells were treated with OPN in vitro [10]. "
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    ABSTRACT: Objectives. Osteopontin (OPN), a multifunctional glycoprotein secreted from a wide variety of cells after inflammatory stimulation, is well accepted to contribute to the development of allergic diseases. However, the influence of histamine H1 receptor antagonists (antihistamines) on OPN functions is not well understood. The present study was undertaken to examine the influence of antihistamines on OPN functions in vitro. Methods. Human nasal epithelial cells (5 × 10(5) cells) were stimulated with 250 ng/mL OPN in the presence of either desloratadine (DL), fexofenadine (FEX), or levocetirizine (LCT). The levels of OPN, GM-CSF, Eotaxin, and RANTES in 24 h culture supernatants were examined by ELISA. The influence of LCT on mRNA expression and transcription factor activation in cells were also examined by real-time RT-PCR and ELISA, respectively. Key Findings. The antihistamines examined significantly suppressed the production of GM-CSF, Eotaxin, and RANTES from cells after OPN stimulation. LCT also exhibited the suppression of mRNA expression for chemokines and transcription factor, NF- κ B and AP-1, activation, which were increased by the stimulation of cells with OPN. Conclusions. The suppressive activity of LCT on OPN functions on nasal epithelial cells may be responsible for the attenuating effect of the agent on allergic diseases.
    12/2013; 2013:735835. DOI:10.1155/2013/735835
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    • "Although T cells are known to produce OPN during bacterial infection [14], the source of OPN in L. monocytogenes infections is unknown. Mast cells release OPN after stimulation with antigen and a range of toll-like receptor (TLR) agonists [15], so could be a potential source. "
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    ABSTRACT: Whilst mast cells participate in the immune defence against the intracellular bacterium , there is conflicting evidence regarding the ability of to infect mast cells. It is known that the pore-forming toxin listeriolysin (LLO) is important for mast cell activation, degranulation and the release of pro-inflammatory cytokines. Mast cells, however, are a potential source of a wide range of cytokines, chemokines and other mediators including osteopontin, which contributes to the clearing of infections , although its source is unknown. We therefore aimed to resolve the controversy of mast cell infection by and investigated the extent of mediator release in response to the bacterium. In this paper we show that the infection of bone marrow-derived mast cells by is inefficient and LLO-independent. LLO, however, is required for calcium-independent mast cell degranulation as well as for the transient and selective downregulation of cell surface CD117 (c-kit) on mast cells. We demonstrate that in addition to the key pro-inflammatory cytokines TNF-α and IL-6, mast cells release a wide range of other mediators in response to . Osteopontin, IL-2, IL-4, IL-13 and granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokines including CCL2, CCL3, CCL4 and CCL5 are released in a MyD88-dependent manner. The wide range of mediators released by mast cells in response to may play an important role in the recruitment and activation of a variety of immune cells . The cocktail of mediators, however, is unlikely to skew the immune response to a particular effector response. We propose that mast cells provide a hitherto unreported source of osteopontin, and may provide an important role in co-ordinating the immune response during infection.
    PLoS ONE 02/2013; 8(2):e57102. DOI:10.1371/journal.pone.0057102 · 3.23 Impact Factor
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