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La segregación dependiente del tamaño controla la fagocitosis de los macrófagos de las dianas con anticuerpos
Matthew H Bakalar1, Aaron M Joffe1, Eva M Schmid2
1Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA; UC Berkeley/UC San Francisco Graduate Group in Bioengineering, Berkeley, CA 94720, USA.
Cell
|June 30, 2018
Resumen
La altura del antígeno es crítica para la fagocitosis de los macrófagos. Los antígenos cortos promueven las respuestas inmunes al permitir el contacto del anticuerpo con el receptor Fc, mejorando la defensa celular contra la enfermedad.
Área de la Ciencia:
- Inmunología
- Biología celular
- La biofísica
Sus antecedentes:
- Los macrófagos son células inmunes cruciales que eliminan las células opsonizadas por anticuerpos a través de la fagocitosis.
- La eficacia de los anticuerpos para desencadenar respuestas inmunes varía, y los mecanismos subyacentes son poco conocidos.
- Se sabe que la estructura y el tamaño del antígeno influyen en la unión de los anticuerpos y en las posteriores interacciones celulares.
Objetivo del estudio:
- Definir un umbral crítico de altura del antígeno que regule la fagocitosis de los macrófagos.
- Para aclarar los mecanismos físicos por los cuales el tamaño del antígeno impacta la señalización del receptor Fc.
- Informar el diseño de anticuerpos terapéuticos más efectivos.
Principales métodos:
- Utilizó un modelo reconstituido de células diana con anticuerpos.
- Tasas de fagocitosis cuantificadas a través de diferentes alturas de antígeno.
- Investigó la segregación espacial de los receptores Fc y la fosfatasa CD45.
- Se evaluó el papel de las integrinas en los eventos de señalización observados.
Principales resultados:
- La fagocitosis se deterioró significativamente cuando los anticuerpos se ubicaron a > 10 nm de la superficie objetivo.
- La disminución de la altura del antígeno promovió la fosforilación del receptor Fc y la fagocitosis.
- Este efecto fue mediado por la segregación independiente de la integrina de los receptores Fc de CD45.
- El contacto cercano entre los macrófagos y las células diana es esencial para una fagocitosis eficiente.
Conclusiones:
- Un umbral de altura del antígeno regula la fagocitosis mediada por los macrófagos.
- Los antígenos cortos facilitan la activación del receptor Fc promoviendo la segregación física de los componentes de señalización.
- Los anticuerpos terapéuticos dirigidos a antígenos cortos pueden mejorar las respuestas inmunes a través de la señalización optimizada de los receptores Fc.
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