Hierarchy of eosinophil chemoattractants: role of p38 mitogen-activated protein kinase.

Schratl, Petra; Sturm, Eva M; Royer, Julia F; Sturm, Gunter J; Lippe, Irmgard T; Peskar, Bernhard A; Heinemann, Akos

Schratl, Petra; Sturm, Eva M; Royer, Julia F; Sturm, Gunter J; Lippe, Irmgard T; Peskar, Bernhard A; Heinemann, Akos.

Afiliación

Schratl P; Institute of Experimental and Clinical Pharmacology, Medical University Graz, Graz, Austria.

Eur J Immunol ; 36(9): 2401-9, 2006 Sep.

Article en En | MEDLINE | ID: mdl-16906532

RESUMEN

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) D2. 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 PGD2 enhancement of eosinophil migrations. In contrast, eotaxin or 5-oxo-ETE inhibited the migration of eosinophils towards PGD2. 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 mitogen-activated protein kinase, and inhibition of p38 mitogen-activated protein kinase by SB-202190 converted the effect of 5-oxo-ETE on the chemotaxis to PGD2 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 PGD2 were unaltered. In conclusion, PGD2 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.

Asunto(s)

Factores Quimiotácticos Eosinófilos/inmunología; Quimiotaxis de Leucocito/inmunología; Eosinófilos/inmunología; Prostaglandina D2/inmunología; Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo; Ácidos Araquidónicos/inmunología; Ácidos Araquidónicos/metabolismo; Carbazoles/farmacología; Quimiocina CCL11; Quimiocinas CC/inmunología; Quimiocinas CC/metabolismo; Factores Quimiotácticos Eosinófilos/metabolismo; Quimiotaxis de Leucocito/efectos de los fármacos; Eosinófilos/efectos de los fármacos; Eosinófilos/metabolismo; Humanos; Inhibidores de Agregación Plaquetaria/farmacología; Prostaglandina D2/metabolismo; Sulfonamidas/farmacología

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prostaglandina D2 / Factores Quimiotácticos Eosinófilos / Quimiotaxis de Leucocito / Proteínas Quinasas p38 Activadas por Mitógenos / Eosinófilos Límite: Humans Idioma: En Revista: Eur J Immunol Año: 2006 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Alemania

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