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

Nagasaka, Akiko; Matsue, Hiroyuki; Matsushima, Hironori; Aoki, Rui; Nakamura, Yuumi; Kambe, Naotomo; Kawa, Shigeyuki; Uede, Toshimitsu; Shimada, Shinji

doi:10.1002/eji.200737057

Cited by 84 publications

(84 citation statements)

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“…OPN's potential involvement in Th2-associated allergic responses has been investigated recently, particularly in eosinophilic airway inflammation [16,17] and in mast cell degranulation [18]. However, its role in systemic allergen sensitization via the production of allergen-specific IgE is still unclear.…”

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confidence: 99%

Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

et al. 2009

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Osteopontin (OPN) is a secreted phosphoglycoprotein with a wide range of functions, and is involved in various pathophysiological conditions. However, the role of OPN in IgE and Th2-associated allergic responses remains incompletely defined. The aim of this study was to elucidate the role of OPN in systemic allergen sensitization in mice. When compared with OPN 1/1 mice, significantly increased levels of OVA-induced IgE were found in OPN À/À mice.OPN À/À DC demonstrated an increased capacity to enhance Th2 cytokine production in CD4 1 T cells from sensitized OPN 1/1 mice. Furthermore, significantly reduced levels of IL-12p70 expression were seen in LPS-stimulated OPN À/À DC as compared with the WT DC, and the reduction was reversible by the addition of recombinant OPN (rOPN). rOPN was able to suppress OVA-induced IL-13 production in the cultures of CD4 and OPN À/À DC, but this inhibitory activity was neutralized by the addition of anti-IL-12 Ab. In addition, administration of rOPN in vivo suppressed OVA-specific IgE production; however, this suppressive effect was abrogated in IL-12-deficient mice. These results indicate that DC-derived OPN plays a regulatory role in the development of systemic allergen sensitization, which is mediated, at least in part, through the production of endogenous IL-12.

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Section: Introductionmentioning

confidence: 99%

Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

et al. 2009

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“…On this background, an additional level of complexity has been uncovered by Nagasaka et al [15], who report in this issue of the European Journal of Immunology that mast cells (MC) need to be entered into the ever-growing league of cells that serve both as sources and as targets of OPN bioactivity (Fig. 1).…”

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“…Nagasaka et al [15] now provide the first evidence that connective tissue-type MC derived from fetal mouse skin, but not bone marrow-derived MC, constitutively transcribe, translate and secrete biologically active OPN in culture. This introduces OPN as an intriguing new player in MC biology and further underscores the wellknown distinctness of skin MC from other members of Eur.…”

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“…Moreover, the authors report that OPN regulates distinct, IgE-dependent murine MC functions [15]. In vitro, OPN augments IgE-mediated MC degranulation via ligand binding to the CD44 and the av integrin receptors, while it regulates the magnitude of an IgEmediated passive cutaneous anaphylaxis reaction in vivo; however, the mode of action and the effector molecules by which OPN executes its regulation of these IgE-dependent MC responses remain to be characterized (Fig.…”

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“…Committed MC progenitors derived from pluripotent stem cells in the bone marrow stroma gain access to the general circulation en route towards their final destination in peripheral tissues [16][17][18]. Now, we learn that OPN can also modulate murine fetal skin-derived MC migration [15]. Irrespectively of its actual cellular source, OPN may thus play a critical role in directing MC progenitors to selected target tissues and in relocating mature MC within tissues and at sites of inflammation.…”

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Osteopontin as a new player in mast cell biology

Bulfone–Paus∥

Paus

2008

Eur J Immunol

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The secreted glycoprotein osteopontin (OPN) sets into motion an astounding variety of activities that range from bone remodeling via immunomodulation to the inhibition of apoptosis. In the current issue of the European Journal of Immunology, OPN now also enters mast cell biology and the regulation of IgE-dependent immune responses since it is reported that connective tissue-type mast cells from fetal murine skin constitutively secrete biologically active OPN. Moreover, it is shown that, in vitro, OPN augments IgEmediated mast cell degranulation and migration via ligand binding to cognate OPN receptors on the mast cell surface (CD44, av integrin) and that the magnitude of an IgEmediated passive cutaneous anaphylaxis reaction is augmented by OPN in vivo. Here, we discuss why this newly discovered property of OPN fits well into the emerging concept that OPN may serve as a multi-purpose environmental damage-response protein.See accompanying article: http://dx.doi.org/10.1002/eji200737057Among the extracellular matrix-associated glycoproteins that increasingly cross the paths of immunologists these days, there are not many that can rival osteopontin (OPN) in terms of complexity and pleiotropy of actions. Since its discovery as a regulator of bone metabolism [1,2], in immunology, OPN has become recognized as a major component of early cellular immune responses during which it predominantly acts as a chemokine-like proinflammatory cytokine [3,4]. It is through a complex series of phosphorylation, glycosylation and proteolytic cleavage events that different functional forms of OPN are produced. OPN exists as a soluble cytokine and as an immobilized protein adsorbed to calcified matrices. While OPN is predominantly a secreted protein, an intracellular form has also been described [5]. It has been proposed that distinct cell types differ in their posttranslational modifications of OPN, which may underlie cell-type specific differences in the functions of OPN [6].In its multiple variations that result from these intricate post-translation modifications, whose controls are only very incompletely understood, this phosphorylated acidic glycoprotein then interacts with many different molecular partners: OPN serves as a substrate for thrombin and matrix metalloproteinases (MMP2, MMP3, MMP7, MMP9 and MMP12), can bind to the extracellular matrix proteins fibronectin and collagen and interacts with integrins a v (b 1 , b 2 , or b 5 ) and (a 4 , a 5 , a 8 or a 9 ) b 1 surface receptors through an Arg-Gly-Asp (RDG) sequence [1,2,6]. In addition, some variants of the hyaluronan CD44 receptor have been identified as a receptor for OPN [6][7][8].

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Prevention of F‐actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells

et al. 2013

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Summary Following antigen/IgE-mediated aggregation of high affinity IgE-receptors (FcεRI), mast cells (MCs) degranulate and release inflammatory mediators leading to the induction of allergic reactions including anaphylaxis. Migration of MCs to resident tissues and sites of inflammation is regulated by tissue chemotactic factors such as stem cell factor (SCF [KIT ligand]). Despite inducing similar early signaling events to antigen, chemotactic factors, including SCF, produce minimal degranulation in the absence of other stimuli. We therefore investigated whether processes regulating MC chemotaxis are rate limiting for MC mediator release. To investigate this issue, we disrupted actin polymerization, a requirement for MC chemotaxis, with latrunculin B and cytochalasin B, then examined chemotaxis and mediator release in human (hu)MCs induced by antigen or SCF. As expected, such disruption minimally affected early signaling pathways, but attenuated SCF-induced huMC chemotaxis. In contrast, SCF, in the absence of other stimuli, induced substantial degranulation in a concentration-dependent manner following actin disassembly. It also moderately enhanced antigen-mediated huMC degranulation which was further enhanced in the presence of SCF. These observations suggest that processes regulating cell migration limit MC degranulation as a consequence of cytoskeletal reorganization.

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

Cited by 84 publications

References 53 publications

Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

Osteopontin as a new player in mast cell biology

Prevention of F‐actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells

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