A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

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A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst. / Royer, J F; Schratl, P; Lorenz, S; Kostenis, E; Ulven, T; Schuligoi, R; Peskar, B A; Heinemann, A.

In: Allergy, Vol. 62, No. 12, 01.12.2007, p. 1401-1409.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Royer, JF, Schratl, P, Lorenz, S, Kostenis, E, Ulven, T, Schuligoi, R, Peskar, BA & Heinemann, A 2007, 'A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst', Allergy, vol. 62, no. 12, pp. 1401-1409. https://doi.org/10.1111/j.1398-9995.2007.01452.x

APA

Royer, J. F., Schratl, P., Lorenz, S., Kostenis, E., Ulven, T., Schuligoi, R., Peskar, B. A., & Heinemann, A. (2007). A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst. Allergy, 62(12), 1401-1409. https://doi.org/10.1111/j.1398-9995.2007.01452.x

Vancouver

Royer JF, Schratl P, Lorenz S, Kostenis E, Ulven T, Schuligoi R et al. A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst. Allergy. 2007 Dec 1;62(12):1401-1409. https://doi.org/10.1111/j.1398-9995.2007.01452.x

Author

Royer, J F ; Schratl, P ; Lorenz, S ; Kostenis, E ; Ulven, T ; Schuligoi, R ; Peskar, B A ; Heinemann, A. / A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst. In: Allergy. 2007 ; Vol. 62, No. 12. pp. 1401-1409.

Bibtex

@article{e6410c6c88b942e9828896af5eff6c2f,
title = "A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst",
abstract = "BACKGROUND: Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) has been revealed to be a novel receptor for prostaglandin (PG) D(2), which is a major mast cell product released during the allergic response. The aim of this study was to analyze the effects of a newly developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast, PGD(2) inhibited the C5a-induced up-regulation of CD63, a cellular marker of degranulation, in a Cay10471-sensitive manner. Finally, Cay10471 abolished the respiratory burst of eosinophils upon stimulation by PGD(2). CONCLUSION: These data further emphasize the importance of CRTH2 in eosinophil function and show that Cay10471 is a highly potent and selective antagonist of PGD(2)-induced eosinophil responses. Cay10471 might hence be a useful compound for the treatment of allergic diseases Udgivelsesdato: Dec",
keywords = "Animals, Bone Marrow, Carbazoles, Cell Degranulation, Cells, Cultured, Chemotaxis, Leukocyte, Eosinophils, Female, Guinea Pigs, Humans, Male, Receptors, Immunologic, Receptors, Prostaglandin, Respiratory Burst, Sulfonamides, Th2 Cells",
author = "Royer, {J F} and P Schratl and S Lorenz and E Kostenis and T Ulven and R Schuligoi and Peskar, {B A} and A Heinemann",
year = "2007",
month = dec,
day = "1",
doi = "10.1111/j.1398-9995.2007.01452.x",
language = "English",
volume = "62",
pages = "1401--1409",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley Online",
number = "12",

}

RIS

TY - JOUR

T1 - A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

AU - Royer, J F

AU - Schratl, P

AU - Lorenz, S

AU - Kostenis, E

AU - Ulven, T

AU - Schuligoi, R

AU - Peskar, B A

AU - Heinemann, A

PY - 2007/12/1

Y1 - 2007/12/1

N2 - BACKGROUND: Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) has been revealed to be a novel receptor for prostaglandin (PG) D(2), which is a major mast cell product released during the allergic response. The aim of this study was to analyze the effects of a newly developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast, PGD(2) inhibited the C5a-induced up-regulation of CD63, a cellular marker of degranulation, in a Cay10471-sensitive manner. Finally, Cay10471 abolished the respiratory burst of eosinophils upon stimulation by PGD(2). CONCLUSION: These data further emphasize the importance of CRTH2 in eosinophil function and show that Cay10471 is a highly potent and selective antagonist of PGD(2)-induced eosinophil responses. Cay10471 might hence be a useful compound for the treatment of allergic diseases Udgivelsesdato: Dec

AB - BACKGROUND: Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) has been revealed to be a novel receptor for prostaglandin (PG) D(2), which is a major mast cell product released during the allergic response. The aim of this study was to analyze the effects of a newly developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast, PGD(2) inhibited the C5a-induced up-regulation of CD63, a cellular marker of degranulation, in a Cay10471-sensitive manner. Finally, Cay10471 abolished the respiratory burst of eosinophils upon stimulation by PGD(2). CONCLUSION: These data further emphasize the importance of CRTH2 in eosinophil function and show that Cay10471 is a highly potent and selective antagonist of PGD(2)-induced eosinophil responses. Cay10471 might hence be a useful compound for the treatment of allergic diseases Udgivelsesdato: Dec

KW - Animals

KW - Bone Marrow

KW - Carbazoles

KW - Cell Degranulation

KW - Cells, Cultured

KW - Chemotaxis, Leukocyte

KW - Eosinophils

KW - Female

KW - Guinea Pigs

KW - Humans

KW - Male

KW - Receptors, Immunologic

KW - Receptors, Prostaglandin

KW - Respiratory Burst

KW - Sulfonamides

KW - Th2 Cells

U2 - 10.1111/j.1398-9995.2007.01452.x

DO - 10.1111/j.1398-9995.2007.01452.x

M3 - Journal article

VL - 62

SP - 1401

EP - 1409

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 12

ER -

ID: 189159448