Release of granule proteins from human eosinophils stimulated with mast‐cell mediators

Takafuji, Shigeru; Tadokoro, Kenji; Itō, Kōji; Nakagawa, Takemasa

doi:10.1111/j.1398-9995.1998.tb03795.x

Cited by 29 publications

(19 citation statements)

References 28 publications

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“…Hence, eotaxin could serve as an end-point chemoattractant also causing degranulation of eosinophils [30]. Notably, PGD 2 and 5-oxo-ETE do not induce eosinophil degranulation [22,42]. Our present data indicate that the complex interplay of chemoattractants at consecutively up-and down-modulating the cells' responsiveness to each other might orchestrate the locomotion of eosinophils over a considerably wide distance, e.g., from the blood stream into the epithelium and alveolar lumen.…”

Section: Discussionmentioning

confidence: 99%

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

et al. 2006

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Several chemoattractants can regulate the recruitment of eosinophils to sites of inflammation, but the hierarchy among them is unknown. We observed here that eosinophil chemotaxis towards eotaxin or 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) was amplified up to sixfold in the presence of prostaglandin (PG) D 2 . This effect was only seen in eosinophils, and not in neutrophils or basophils. Pretreatment with the chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) antagonist ramatroban prevented the PGD 2 enhancement of eosinophil migrations. In contrast, eotaxin or 5-oxo-ETE inhibited the migration of eosinophils towards PGD 2 . 5-oxo-ETE enhanced the chemotaxis to eotaxin, while eotaxin had no effect on 5-oxo-ETE-induced migration. 5-oxo-ETE induced the phosphorylation of p38 mitogenactivated protein kinase, and inhibition of p38 mitogen-activated protein kinase by SB-202190 converted the effect of 5-oxo-ETE on the chemotaxis to PGD 2 from inhibition to enhancement. The presence of blood or plasma markedly decreased the sensitivity of eosinophils to eotaxin or 5-oxo-ETE, while responses to PGD 2 were unaltered. In conclusion, PGD 2 might be an initial chemoattractant, since it maintains its potency in the circulation and augments the responsiveness of eosinophils to other chemoattractants. In contrast, eotaxin seems to be an end-point chemoattractant, since it has reduced efficacy in blood and is capable of down-modulating eosinophil responsiveness to other chemoattractants. IntroductionAccumulation of eosinophils at sites of allergic reactions, such as eczema or asthma, is associated with tissue injury and lung dysfunction [1]. It has been shown recently that asthmatic patients that received treatment based on eosinophil counts in sputum had significantly fewer severe asthma exacerbations than patients treated according to standard management therapy [2]. Moreover, genetically modified mice lacking eosinophils are protected against allergen-induced lung injury and asthma [3,4].Although several chemoattractants can mediate eosinophil recruitment, none of them could be identified so far as a predominating factor governing eosinophil infiltration, suggesting a co-operative action of multiple chemoattractants in disease. Among these are the CC-chemokines, such as eotaxin, RANTES, or MCP-4 acting through the chemokine receptor CCR3 [5,6]. Prostaglandin (PG) D 2 , a major mast cell mediator released during the allergic response [7] might be of particular importance, since PGD 2 is capable of inducing the chemotaxis of eosinophils, basophils and Th2-type * These authors contributed equally to this study. T cells via a novel receptor, chemoattractant receptorhomologous molecule expressed on TH2 cells (CRTH2) [8,9]. Besides chemotaxis, we have shown that activation of CRTH2 also causes eosinophil respiratory burst and the release of eosinophils from the bone marrow [10]. In vivo, PGD 2 can induce pulmonary eosinophilia [11], and a significant contribution of PGD 2 to the late phase allergi...

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Section: Discussionmentioning

confidence: 99%

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

et al. 2006

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“…Chymase, a mast cell-specific protease, and PAF can also regulate eosinophil infiltration, activation and degranulation [54,55]. Tryptase, the other mast cell preformed neutral protease, is capable as well of activating and degranulating eosinophils through binding to the protease-activated receptor PAR2 on eosinophils [28,56].…”

Section: Mast Cells and Eosinophils The Two Components Of ''The Allementioning

confidence: 99%

Mast cells and eosinophils: the two key effector cells in allergic inflammation

2009

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The allergic inflammatory response is composed of two main phases--the early and the late. The early phase initiates when an allergen activates the tissue resident mast cell, triggering the release of a variety of granule-stored and newly formed mediators. As the inflammatory response progresses, blood borne inflammatory cells--in particular, eosinophils--are recruited into the inflamed tissue. Eosinophil activation and consequent release and production of several pro-inflammatory mediators results in the late phase reaction. A chronic allergic inflammation always features prominent tissue eosinophilia. In this review, we will discuss the possible channels of communication, both soluble and physical, between mast cells and eosinophils that can occur in the late and chronic stages of allergy. Such interactions, that we have termed "the allergic effector unit", may modulate the severity and/or duration of the allergic inflammatory reaction.

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“…It has been reported that PGD 2 not only increases cytosolic calcium in eosinophils [1]but also primes eosinophils for enhanced release of LTC 4 in response to the calcium ionophore A23187 [2]. In this study, PGD 2 induced ECP release in IL-3-primed eosinophils.…”

Section: Resultsmentioning

confidence: 52%

“…Human eosinophils were purified from venous blood of informed healthy volunteers by 2-step density centrifugation plus negative selection as described previously [1]. Seratrodast was the kind gift from Takeda Pharmaceuticals Co. (Osaka, Japan).…”

Section: Methodsmentioning

confidence: 99%

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Eosinophil Activation by Prostaglandin D<sub>2</sub> and Its Modulation by Seratrodast

Takafuji

Miyakuni

Hirai³

et al. 2001

Int Arch Allergy Immunol

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Background: Seratrodast is one of the antiallergic drugs and causes antagonism not only to thromboxane A₂ but also to prostaglandin D₂ (PGD₂). It has been reported that PGD₂ increases cytosolic free calcium concentration ([Ca²⁺]i) in human eosinophils. In this study, we have examined the effect of seratrodast on eosinophil cationic protein (ECP) release and changes of [Ca²⁺]i in human eosinophils induced by PGD₂. Methods: Eosinophils from healthy donors were incubated with or without IL-3 for 10 min after incubation with or without seratrodast for 15 min. Then, they were stimulated with PGD₂ for 20 min after incubation with cytochalasin B for 10 min. Results: PGD₂ induced significant ECP release in IL-3-primed eosinophils. This ECP release was significantly inhibited by seratrodast. Seratrodast had no effect on ECP release induced by PAF in IL-3-primed eosinophils. Furthermore, pretreatment with seratrodast inhibited cytosolic calcium increase induced by PGD₂ in human eosinophils, and it had no effect on that induced by PAF. Conclusions: This study shows that PGD₂ induces ECP release in IL-3-primed eosinophils and that seratrodast suppresses its effect. This inhibition by seratrodast may contribute to its clinical efficacy in the treatment of bronchial asthma.

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Release of granule proteins from human eosinophils stimulated with mast‐cell mediators

Abstract: Of mast-cell mediators, LTB4 and PAF induced eosinophil degranulation. The contribution of LTB4 and PAF from mast cells to eosinophil degranulation may be important in the pathogenesis of allergic inflammatory diseases.

Cited by 29 publications

References 28 publications

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

Mast cells and eosinophils: the two key effector cells in allergic inflammation

Eosinophil Activation by Prostaglandin D<sub>2</sub> and Its Modulation by Seratrodast

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