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VCAM-1 en el endotelio activado interactúa con la integrina leucocitaria VLA-4 en un sitio distinto del sitio de

M J Elices¹, L Osborn, Y Takada

¹Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

|February 23, 1990

Resumen

La integrina VLA-4 actúa como un receptor para la molécula de adhesión celular vascular-1 (VCAM-1), mediando la adhesión de los linfocitos. Esta interacción es crucial para reclutar leucocitos mononucleares a los sitios inflamatorios.

Área de la Ciencia:

Inmunología Inmunología.
Biología celular Biología celular.
La medicina molecular es una medicina molecular.

Sus antecedentes:

Las células endoteliales activadas por citocinas expresan la molécula de adhesión celular vascular 1 (VCAM-1).
VCAM-1 juega un papel en la unión de los linfocitos.
Comprender el receptor VCAM-1 es clave para el tráfico de células inmunes.

Objetivo del estudio:

Para identificar el receptor específico para VCAM-1 en los linfocitos.
Para dilucidar las interacciones moleculares que gobiernan la adhesión celular mediada por VCAM-1.
Para diferenciar las interacciones de VLA-4 con VCAM-1 y la fibronectina.

Principales métodos:

Transfección de las células K-562 con la subunidad cDNA de VLA-4 alfa 4.
Evaluación de la adhesión celular al VCAM-1 y a la fibronectina.
El uso de anticuerpos anti-VLA-4 y fragmentos de fibronectina soluble para estudios de inhibición.

Principales resultados:

VLA-4 (antigeno muy tardío-4) fue identificado como el receptor específico para VCAM-1.
La expresión de VLA-4 en las células K-562 medió la adhesión específica a VCAM-1.
VLA-4 también medió la adhesión a la región de unión a la heparina II (FN-40) de la fibronectina.
Las interacciones VLA-4/VCAM-1 y VLA-4/fibronectina se distinguieron por inhibidores específicos.

Conclusiones:

Se ha identificado la pareja ligando-receptor VLA-4/VCAM-1.
Esta interacción es significativa para el reclutamiento de leucocitos mononucleares a los sitios inflamatorios.
VLA-4 exhibe distintas propiedades de unión a VCAM-1 y a la fibronectina.

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