The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane

Navarro, Susanna; Aleu, Jordi; Jiménez, M.; Boix, Ester; Cuchillo, Claudi M.; Nogués, M. Victòria

doi:10.1007/s00018-007-7499-7

Cited by 78 publications

(73 citation statements)

References 43 publications

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“…This eosinophil protein has been described for its tumoricidal effect (46)(47)(48)(49) and pore membrane-forming properties (50,51). A recent study showed that ECP was not internalized (52). Membrane immunofluorescence pathway of ECP released during coculture was consistent with a pore-forming effect.…”

Section: Discussionmentioning

confidence: 83%

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

Legrand

Driss

Delbeke

et al. 2010

The Journal of Immunology

149

135

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Peripheral blood and tissue eosinophilia is a prominent feature in allergic diseases and helminth infections. In cancer patients, tumor-associated tissue eosinophilia is frequently observed. Tumor-associated tissue eosinophilia can be associated with a favorable prognosis, notably in colorectal carcinoma. However, underlying mechanisms of eosinophil contribution to antitumor responses are poorly understood. We have in this study investigated the direct interactions of human eosinophils with Colo-205, a colorectal carcinoma cell line, and show that eosinophils induce apoptosis and directly kill tumor cells. Using blocking Abs, we found that CD11a/CD18 complex is involved in the tumoricidal activity. Coculture of eosinophils with Colo-205 led to the release of eosinophil cationic protein and eosinophil-derived neurotoxin as well as TNF-α secretion. Moreover, eosinophils expressed granzyme A, which was released upon interaction with Colo-205, whereas cytotoxicity was partially inhibited by FUT-175, an inhibitor of trypsin-like enzymatic activity. Our data present the first demonstration, to our knowledge, that granzyme A is a cytotoxic mediator of the eosinophil protein arsenal, exerting eosinophil tumoricidal activity toward Colo-205, and provide mechanistic evidence for innate responses of eosinophil against tumor cells.

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Section: Discussionmentioning

confidence: 83%

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

Legrand

Driss

Delbeke

et al. 2010

The Journal of Immunology

149

135

View full text Add to dashboard Cite

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“…ECP has been found to attach to cell membrane altering permeability as well as increasing production of reactive oxygen species [Navarro et al 2008]. MBP was also found to cause alveolar epithelium cell lysis allowing for penetration of inhaled antigen [Ayars et al 1985].…”

Section: Introductionmentioning

confidence: 99%

Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

George

Brightling²

2015

Therapeutic Advances in Chronic Disease

268

188

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Abstract:The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments.

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“…The infiltrating eosinophils release several toxic and proinflammatory mediators which induce epithelial injury, airway hyper-responsiveness, and airway remodeling [6][7][8]. Therefore, eosinophils are regarded as potential therapeutic targets in allergic diseases and asthma [9].…”

Section: Introductionmentioning

confidence: 99%

Interaction of eosinophils with endothelial cells is modulated by prostaglandin EP4 receptors

et al. 2011

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Eosinophil extravasation across the endothelium is a key feature of allergic inflammation. Here, we investigated the role of PGE 2 and its receptor, E-type prostanoid receptor (EP)-4, in the regulation of eosinophil interaction with human pulmonary microvascular endothelial cells. PGE 2 and the EP4 receptor agonist ONO AE1-329 significantly reduced eotaxininduced eosinophil adhesion to fibronectin, and formation of filamentous actin and gelsolin-rich adhesive structures. These inhibitory effects were reversed by a selective EP4 receptor antagonist, ONO AE3-208. PGE 2 and the EP4 agonist prevented the activation and cell-surface clustering of b2 integrins, and L-selectin shedding of eosinophils. Under physiological flow conditions, eosinophils that were treated with the EP4 agonist showed reduced adhesion to endothelial monolayers upon stimulation with eotaxin, as well as after TNF-a-induced activation of the endothelial cells. Selective activation of EP1, EP2, and EP3 receptors did not alter eosinophil adhesion to endothelial cells, whereas the EP4 antagonist prevented PGE 2 from decreasing eosinophil adhesion. Finally, eosinophil transmigration across thrombin-and TNF-a-activated endothelial cells was effectively reduced by the EP4 agonist. These data suggest that PGE 2 -EP4 signaling might be protective against allergic responses by inhibiting the interaction of eosinophils with the endothelium and might hence be a useful therapeutic option for controlling inappropriate eosinophil infiltration.Keywords: Adhesion . Endothelium . Eosinophils . Migration . Prostaglandins Supporting Information available online IntroductionEosinophil granulocytes are important effector cells in allergic inflammation and are recruited to the tissue by chemotactic signals [1][2][3][4][5]. The infiltrating eosinophils release several toxic and proinflammatory mediators which induce epithelial injury, airway hyper-responsiveness, and airway remodeling [6][7][8]. Therefore, eosinophils are regarded as potential therapeutic targets in allergic diseases and asthma [9].Prostaglandins (PGs) play diverse roles in inflammation, depending on the cellular context, the type of PG being released, and the differential expression of PG receptors [10,11]. While PGD 2, which is the predominant PG formed in mast cells, exerts proinflammatory effects by regulating the recruitment of eosino- Eur. J. Immunol. 2011. 41: 2379-2389 DOI 10.1002 Leukocyte signaling 2379 phils, basophils, and Th2 lymphocytes to the sites of allergic inflammation [12], PGE 2 seems to attenuate inflammatory responses and reduce tissue injury in airways [13]. PGE 2 was found to exert bronchoprotective effects in patients with asthma [14]. In rats, the ovalbumin-induced early and late phase airway responses were inhibited by intratracheally administered PGE 2 [15]. The activity of PGE 2 is mediated by four subtypes of E-type prostanoid receptors (EP), EP1, EP2, EP3, and EP4 [16]. These G protein-coupled receptors have distinct biological imprints depending on their affinity with...

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The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane

Cited by 78 publications

References 43 publications

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

Interaction of eosinophils with endothelial cells is modulated by prostaglandin EP4 receptors

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