Eosinophil-eicosanoid interactions: inhibition of eosinophil chemotaxis in vivo by a LTD4-receptor antagonist

Chen, Chan; McKee, Katherine; Tagari, Philip; Chee, P.; Ford‐Hutchinson, A. W.

doi:10.1016/0014-2999(90)94159-u

Cited by 53 publications

(9 citation statements)

References 15 publications

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“…Bronchoprovocation studies [2, 3, 4, 5, 6, 7, 8]as well as recent clinical trials with different classes of CysLT 1 antagonists and a 5-lipoxygenase inhibitor [9, 10, 11, 12, 13, 14, 15]have provided evidence to support a role for CysLTs in inducing persistent eosinophilia in the airway and peripheral blood of asthmatic patients. Inhaled LTC 4 and/or LTD 4 caused eosinophil infiltration of the airway in the guinea pig, which was blocked by the CysLT 1 antagonist MK-571 [3]or zafirlukast [4].…”

Section: Introductionmentioning

confidence: 99%

A Functional Study on CysLT1 Receptors in Human Eosinophils

Ohshima¹,

Nagase²,

Koshino³

et al. 2002

Int Arch Allergy Immunol

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Background: The cysteinyl leukotrienes (CysLTs) mediate their biological actions through two receptors: CysLT₁ receptor and CysLT₂ receptor. Objective: This study was undertaken to examine the direct effects of CysLTs on eosinophils, such as chemotaxis and degranulation, focusing on CysLT₁. Methods: Eosinophils were isolated from venous blood from normal volunteers who had no history of allergy (purity >99%). They were subjected to reverse transcription-PCR analysis and flow-cytometric analysis for CysLT₁. Binding assays were performed with [³H]LTD₄. Purified eosinophils loaded with Fura-2 acetoxymethyl ester were stimulated with CysLTs, and Ca²⁺ influx was measured. Eosinophil migration in response to CysLTs was measured using a 96-well multiwell Boyden chamber. Eosinophils were treated with LTD₄ at 10^–6M for 60 min followed by incubation for 4 h at 37°C in the presence or absence of IL-5 and eosinophil-derived neurotoxin (EDN) release was evaluated. Results: The expression of the mRNA and protein of CysLT₁ on eosinophils and [³H]LTD₄-specific binding to eosinophils were observed. Neither Th1 cytokine (IFN-γ) nor Th2 cytokines (IL-4 or IL-5) affected CysLT₁ expression in eosinophils. CysLTs induced an increase in intracellular free Ca²⁺ in eosinophils via CysLT₁, as suggested by the efficient inhibition by a CysLT₁ antagonist, pranlukast, in addition to the rank order of potency being LTD₄, LTC₄ and LTE₄. LTD₄ stimulated eosinophils to migrate at 10^–6M via CysLT₁. LTE₄ also induced significant eosinophil migration at 10^–6M. LTD₄ enhanced EDN release induced by IL-5 via CysLT₁. Conclusion: CysLTs induce migration and enhance degranulation in eosinophils via CysLT₁. Accordingly, interaction of CysLTs and CysLT₁ on eosinophils has the potential to play a prominent role in the pathophysiology of asthma.

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Section: Introductionmentioning

confidence: 99%

A Functional Study on CysLT1 Receptors in Human Eosinophils

Ohshima¹,

Nagase²,

Koshino³

et al. 2002

Int Arch Allergy Immunol

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“…Additional but not as well-established effect is the ability of cysteinyl LTs to control eosinophil activities, including those related to tissue infiltration. Involvement of cysteinyl LTs in eosinophil influx is an in vivo phenomenon which was firstly demonstrated in guinea-pigs (Chan et al, 1990), but also observed in human (Laitinen et al, 1993) and reinforced by the anti-allergic effects of CysLT1 antagonists which, in addition to inhibiting allergic symptoms, also inhibit eosinophil recruitment during airway allergic inflammation (Peters-Golden, 2008). Even though cysteinyl LTs display negligible eosinophilotactic activity in vitro ( Figure 1 , left panel; Fregonese et al, 2002), cysteinyl LTs contribute to several mechanisms involved in mouting tissue eosinophilia, since: (i) cysteinyl receptor CysLT1 appears to play a role in eosinophilopoeisis, inasmuch as CysLT1 antagonism in vivo limits IL-5-responsive eosinophil differentiation and maturation (Saito et al, 2004); (ii) cysteinyl LTs are able to significantly up-regulate adhesion molecules, such as Mac-1 expression (Fregonese et al, 2002; Saito et al, 2004); (iii) direct administration of LTC 4 induce a rapid and significant reduction in leukocyte rolling velocity, further increasing cell adherence odds (Kanwar et al, 1995); (iv) cysteinyl LTs induce RANTES production from isolated lung cells, which in turn might cause RANTES-driven migration of eosinophils into airways (Kawano et al, 2003).…”

Section: How Do Lipid Mediators Impact Eosinophil Migration?mentioning

confidence: 99%

Eosinophil recruitment and activation: the role of lipid mediators

Luna-Gomes¹,

Bozza²,

Bandeira‐Melo³

2013

Front. Pharmacol.

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Eosinophils are effector cells that migrate toward several mediators released at inflammatory sites to perform their multiple functions. The mechanisms driving eosinophil selective accumulation in sites of allergic inflammation are well-established and involve several steps controlled by adhesion molecules, priming agents, chemotactic, and surviving factors. Even though the majority of studies focused on role of protein mediators like IL-5 and eotaxins, lipid mediators also participate in eosinophil recruitment and activation. Among the lipid mediators with distinguish eosinophil recruitment and activation capabilities are platelet activating factor and the eicosanoids, including leukotriene B4, cysteinyl leukotrienes, and prostaglandin D2. In this review, we focused on the role of these four lipid mediators in eosinophil recruitment and activation, since they are recognized as key mediators of eosinophilic inflammatory responses.

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“…Various studies have been performed to investigate the mechanisms involved in the migration of 111 In–labelled leukocytes to areas of inflammation [15, 16, 20, 21, 24]. Teixeira et al [24]found that the accumulation of neutrophils and eosinophils at inflammatory sites in guinea–pig skin involves the leukocyte adhesion molecule, the β 2 –integrin, CD18.…”

Section: Discussionmentioning

confidence: 99%

“…Chan et al [20]demonstrated that topical application of both antigen and LTD 4 can induce late eosinophil migration in the guinea–pig conjunctiva. Intradermal injection of different known mediators of inflammation to guinea–pigs leads to a dose–dependent accumulation of 111 In–labelled eosinophils or neutrophils in the skin and local oedema formation [21, 22, 23, 24].…”

Section: Introductionmentioning

confidence: 99%

111In–Labelled Leukocyte Migration to the Lungs of Ovalbumin–Sensitized Guinea–Pigs after Aerosol Challenge with Ovalbumin Monitored by Gamma Scintigraphy

Lewis¹,

Warren

Broadley³

1999

Int Arch Allergy Immunol

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Background: To determine whether antigen challenge is associated with increased accumulation of leukocytes in the lungs, the pulmonary accumulation of ¹¹¹In–labelled neutrophils and eosinophils was monitored by gamma scintigraphy. Methods: Guinea–pigs were sensitized with ovalbumin (OA) 14–21 days before challenge with aerosolized OA (10 mg/ml) for 2 min, and protected against fatal anaphylaxis by mepyramine (30 mg/kg). Comparisons were made with OA–sensitized guinea–pigs challenged with saline. 5 or 24 h following the OA challenge, guinea–pigs were anaesthetized and the jugular vein and right carotid artery were cannulated, with the contralateral artery tied off. 2MBq ^99mTc macroaggregated albumin (MAA) was injected intravenously to create a pulmonary perfusion image as a template for the lungs. ¹¹¹In–labelled neutrophils or eosinophils were then injected via the carotid artery and gamma scintigraphic images obtained. Activity in the lung region of each animal was determined by superimposing the ^99mTcMAA image of the lungs on the whole body image. Results: A significant increase in activitiy (p<0.05) in the lung region was observed after injection of ¹¹¹In–labelled neutrophils at 5 h after the OA challenge compared with saline challenge. 24 h after OA challenge there was a significant increase in activity (p<0.05) in the lung region after injection of ¹¹¹In–labelled eosinophils, but no change in activity after injection of labelled neutrophils compared with the saline–challenged animals. Conclusion: This technique models the migration of leukocyte to the lungs seen in guinea–pigs in our previous studies, namely an eosinophilia at 24 h and a neutrophilia at 5 h after OA challenge. It will therefore be useful for investigating anti–inflammatory drugs on the airways.

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Eosinophil-eicosanoid interactions: inhibition of eosinophil chemotaxis in vivo by a LTD4-receptor antagonist

Cited by 53 publications

References 15 publications

A Functional Study on CysLT<sub>1</sub> Receptors in Human Eosinophils

A Functional Study on CysLT<sub>1</sub> Receptors in Human Eosinophils

Eosinophil recruitment and activation: the role of lipid mediators

<sup>111</sup>In–Labelled Leukocyte Migration to the Lungs of Ovalbumin–Sensitized Guinea–Pigs after Aerosol Challenge with Ovalbumin Monitored by Gamma Scintigraphy

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