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Dominant role of L- and P-selectin in mediating CXC chemokine-induced neutrophil migration in vivo.
Miotla, J M; Ridger, V C; Hellewell, P G.
Afiliación
  • Miotla JM; Endothelial Cell Biology Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX.
Br J Pharmacol ; 133(4): 550-6, 2001 Jun.
Article en En | MEDLINE | ID: mdl-11399672
The role of selectins in neutrophil emigration in response to the CXC chemokines KC and MIP-2 was investigated in wild type and P-selectin deficient mice. Intrapleural injection of KC or MIP-2 induced a rapid and specific neutrophil accumulation. Emigration 2 h after KC or MIP-2 was reduced 83 - 88% by anti-L-selectin mAb and 53 - 63% by anti-P-selectin mAb. Co-administration of anti-L- and P-selectin mAbs abolished neutrophil migration induced by either chemokine. An anti-E-selectin mAb tested alone did not affect KC-induced neutrophil migration after 2 or 4 h. Moreover, anti-E-selectin did not have an additive inhibitory effect on KC-induced neutrophil migration compared with P-selectin blockade alone. This was found when neutrophil migration was measured at 2 and 4 h after KC. Despite a blood neutrophilia, neutrophil migration at 2 and 4 h after KC was markedly smaller (by approximately 90%) in P-selectin deficient mice compared with wild type animals. Responses at both time points were not decreased further in animals given E-selectin mAb but were reduced to the PBS control level in the presence of anti-L-selectin. In vitro study of cultured murine endothelial cells demonstrated that KC can directly increase cell surface P-selectin expression. These data suggest that CXC chemokine-induced neutrophil accumulation is dependent on both neutrophil L-selectin and a rapid upregulation of endothelial P-selectin but there is no evidence for E-selectin induction.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Movimiento Celular / Selectina-P / Selectina L / Quimiocinas CXC / Péptidos y Proteínas de Señalización Intercelular / Neutrófilos Límite: Animals Idioma: En Revista: Br J Pharmacol Año: 2001 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Movimiento Celular / Selectina-P / Selectina L / Quimiocinas CXC / Péptidos y Proteínas de Señalización Intercelular / Neutrófilos Límite: Animals Idioma: En Revista: Br J Pharmacol Año: 2001 Tipo del documento: Article Pais de publicación: Reino Unido