Carbon nanotube recognition by human Siglec-14 provokes inflammation.
Nat Nanotechnol
; 18(6): 628-636, 2023 Jun.
Article
en En
| MEDLINE
| ID: mdl-37024598
ABSTRACT
For the design and development of innovative carbon nanotube (CNT)-based tools and applications, an understanding of the molecular interactions between CNTs and biological systems is essential. In this study, a three-dimensional protein-structure-based in silico screen identified the paired immune receptors, sialic acid immunoglobulin-like binding lectin-5 (Siglec-5) and Siglec-14, as CNT-recognizing receptors. Molecular dynamics simulations showed the spatiotemporally stable association of aromatic residues on the extracellular loop of Siglec-5 with CNTs. Siglec-14 mediated spleen tyrosine kinase (Syk)-dependent phagocytosis of multiwalled CNTs and the subsequent secretion of interleukin-1ß from human monocytes. Ectopic in vivo expression of human Siglec-14 on mouse alveolar macrophages resulted in enhanced recognition of multiwalled CNTs and exacerbated pulmonary inflammation. Furthermore, fostamatinib, a Syk inhibitor, blocked Siglec-14-mediated proinflammatory responses. These results indicate that Siglec-14 is a human activating receptor recognizing CNTs and that blockade of Siglec-14 and the Syk pathway may overcome CNT-induced inflammation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Nanotubos de Carbono
/
Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Nanotechnol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón