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El canal K+ activado por Ca2+ de gran conductividad es esencial para la inmunidad innata
Jatinder Ahluwalia1, Andrew Tinker, Lucie H Clapp
1Department of Medicine University College London, Gower Street, London WC1E 6BT, UK.
Nature
|February 27, 2004
Resumen
Los neutrófilos matan a los microbios utilizando proteasas activadas por un canal potásico específico. El bloqueo de este canal de potasio activado por calcio (BK ((Ca)) de gran conductividad evita la muerte microbiana, revelando su papel esencial en la inmunidad innata.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Fisiología del canal iónico Fisiología del canal iónico
Sus antecedentes:
- Los neutrófilos son actores clave en la inmunidad innata, tradicionalmente se pensaba que mataban a los microbios principalmente a través de especies reactivas de oxígeno (ROS).
- La evidencia emergente sugiere que las proteasas, activadas por un ambiente de vacío fagocítico generado por la oxidasa, también pueden ser cruciales para la matanza microbiana.
Objetivo del estudio:
- Investigar el papel del flujo de potasio (K+) y los canales K+ (BK(Ca)) activados por Ca2+ de gran conductividad en la matanza microbiana mediada por neutrófilos.
- Para determinar si los canales BK (Ca) son esenciales para la actividad microbicida de los neutrófilos.
Principales métodos:
- Se utilizaron inhibidores específicos de los canales BK (Ca) (iberiotoxina, paxilina) y un abridor (NS1619) para evaluar sus efectos sobre los flujos 86Rb+ inducidos por la oxidasa y la alcalinización de la vacuola fagocítica.
- Las grabaciones electrofisiológicas demostraron corrientes de K+ en neutrófilos y eosinófilos.
- El bloqueo occidental confirmó la expresión del canal BK subunidad alfa.
Principales resultados:
- Los inhibidores de los canales BK (Ca) bloqueaban el flujo de K+ inducido por la oxidasa y la alcalinización del vacío, mientras que un abridor mejoraba estos procesos.
- La iberiotoxina inhibió de manera reversible las corrientes K+ características en los neutrófilos y los eosinófilos.
- El bloqueo de los canales BK(Ca) abolió por completo la matanza microbiana y la digestión por los neutrófilos.
Conclusiones:
- Los canales K+ (BK(Ca)) activados por Ca2+ de gran conductividad facilitan el eflujo de K+ hacia las vacuolas fagocíticas, contribuyendo a la alcalinización requerida para la activación de la proteasa.
- Estos canales BK(Ca) son esenciales para la actividad microbicida de los neutrófilos, lo que representa un nuevo mecanismo más allá de la producción de ROS.
- Dirigirse a los canales de BK (Ca) podría ofrecer nuevas estrategias terapéuticas para las enfermedades infecciosas.
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