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 FcepsilonRI 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 alphav). 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.

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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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    • "Osteopontin, also known as early T-cell activation protein of gene-1 product, is a secreted 314 amino acid pleiotropic broadly expressed phosphoglycoprotein that exists both as a component of the non-collagenous bone matrix to regulate biomineralization in the bone tissue, and as a soluble cytokine (Wesson et al., 2003). Osteopontin is not only present in the bone, but is also produced by a number of cell types including immune cells (such as mast cells, activated macrophages, leukocytes and activated T lymphocytes ), chondrocytes, smooth muscle cells, epithelial cells, and endothelial cells (Denhardt et al., 2001; Nagasaka et al., 2008; Braitch and Constantinescu, 2010; Samitas et al., 2011). Osteopontin participates in wide range of biological processes, including bone remodeling, cancer and immunity to infectious disease (Denhardt et al., 2001; Gravallese, 2003; Zhao et al., 2011). "
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    ABSTRACT: Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls (P<0.001). Increased serum osteopontin levels were found in 80.95% (34/42) of autistic children. Children with severe autism had significantly higher serum osteopontin levels than patients with mild to moderate autism (P=0.02). Moreover, serum osteopontin levels of autistic patients had significant positive correlations with CARS (P=0.007). In conclusions, serum osteopontin levels were increased in many autistic children and they were significantly correlated to the severity of autism. Further wide-scale studies are warranted to shed light on the etiopathogenic role of osteopontin in autism and to investigate its relation to IL-17 and brain-specific auto-antibodies, which are indicators of autoimmunity, in these patients. The therapeutic role of anti-osteopontin antibodies in amelioration of autistic manifestations should also be studied.
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    • "ease in osteopontin was observed in the hearts of CeO 2 instilled C57BL / 6 . Osteopontin is reported to play a role in the patho - genesis of inflammatory and immune - mediated dis - eases ( Wang and Denhardt 2008 ) and more recently has been identified as a novel mast cell mediator which is produced by mast cells ( Bulfone - Paus and Paus 2008 ; Nagasaka et al . 2008 ) . Serum osteopontin levels are proposed as a biomarker for pneumoconi - osis since an increase in osteopontin has been observed in asbestosis patients compared to healthy controls ( Park et al . 2009 ) . Osteopontin may influ - ence the inflammatory response to particle exposure through increased recruitment of inflammatory cells such"
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