CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.
Blood
; 130(19): 2092-2100, 2017 11 09.
Article
em En
| MEDLINE
| ID: mdl-28807980
ABSTRACT
CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with ß2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting a role in neutrophil migration. However, CD177pos neutrophils exhibit no clear migratory advantage in vivo, despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177pos and CD177neg neutrophils migrated comparably. CD177 ligation selectively impaired migration of CD177pos neutrophils, an effect mediated through immobilization and cellular spreading on the transwell membrane. Correspondingly, CD177 ligation enhanced its interaction with ß2 integrins, as revealed by fluorescence lifetime imaging microscopy, leading to integrin-mediated phosphorylation of Src and extracellular signal-regulated kinase (ERK). CD177-driven cell activation enhanced surface ß2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. We conclude that CD177 signals in a ß2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Superfície Celular
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Antígenos CD18
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Quimiocinas
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Sistema de Sinalização das MAP Quinases
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Migração Transendotelial e Transepitelial
/
Isoantígenos
/
Neutrófilos
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Blood
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Marrocos