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Mac-1 (CD11b/CD18) vincula la inflamación y la trombosis después de una lesión glomerular
Junichi Hirahashi1, Keiichi Hishikawa, Shinya Kaname
1Brigham and Women's Hospital, Department of Pathology, 77 Avenue Louis Pasteur, NRB752O, Boston, MA 02115, USA.
Circulation
|September 16, 2009
Resumen
La integrina Mac-1 de los leucocitos es un vínculo clave entre la inflamación y la trombosis. Dirigirse a Mac-1 puede ofrecer nuevas terapias antitrombóticas para afecciones como la glomerulonefritis trombótica.
Área de la Ciencia:
- Nefrología Nefrología.
- Inmunología Inmunología.
- Hematología Hematología.
Sus antecedentes:
- La inflamación y la trombosis frecuentemente ocurren juntas en varias enfermedades.
- Se sabe que los leucocitos promueven la coagulación de la sangre en los sitios inflamatorios, pero los mecanismos moleculares clave no están claros.
Objetivo del estudio:
- Para investigar los mecanismos moleculares que vinculan la inflamación y la trombosis.
- Para aclarar el papel de las integrinas leucocitarias en la glomerulonefritis trombótica (TGN).
Principales métodos:
- Desarrolló un modelo murino de glomerulonefritis trombótica (TGN).
- Utilizó el agotamiento de neutrófilos y ratones con deficiencia de Mac-1.
- Se evaluó el reclutamiento de neutrófilos, la lesión endotelial, la trombosis y la función renal.
- Investigó el papel de la elastasa de los neutrófilos y las interacciones plaquetarias.
Principales resultados:
- La deficiencia de Mac-1 atenuó notablemente el reclutamiento de neutrófilos, la lesión endotelial, la trombosis glomerular y la insuficiencia renal aguda en TGN.
- La elastasa de neutrófilos fue identificada como un probable efector Mac-1.
- La deposición inicial de plaquetas protegió contra lesiones graves, mientras que la trombosis mediada por Mac-1 siguió.
Conclusiones:
- La integrina leucocitaria Mac-1 es un enlace molecular crítico entre la inflamación y la trombosis.
- Mac-1 representa un objetivo terapéutico potencial para las estrategias antitrombóticas.
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