The chemorepellent Slit3 promotes monocyte migration.
J Immunol
; 185(12): 7691-8, 2010 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-21078908
Directional migration is an essential step for monocytes to infiltrate sites of inflammation, a process primarily regulated by chemoattractants. Slits are large matrix proteins that are secreted by endothelial cells; they were reported to inhibit the chemoattractant-induced migration of different cell types, including leukocytes. The aim of this study was to determine the effect of Slit3 on primary monocyte migration and to address the underlying mechanisms. We show that Roundabout (Robo)1, one of the Robo receptors that recognize Slit3, is the only Robo homolog expressed by CD14(+) monocytes. Interestingly, we found that stimulation with Slit3 increased the spontaneous and chemoattractant-induced migration of primary monocytes in vitro and increased the myeloid cell recruitment during peritoneal inflammation in vivo. In addition, Slit3 did not seem to act as a chemoattractant itself; it promoted directed migration triggered by chemoattractants, such as CXCL12, by inducing a chemokinetic effect. We further show that Slit3 prevented monocyte spreading and induced rounding of spread monocytes without affecting monocyte adhesion. Stimulation with Slit3 was not associated with changes in the levels of phosphorylated p38, p42/p44, or Src, known regulators of monocyte migration, but it directly acts on molecular pathways involved in basal leukocyte migration by activating RhoA. These findings show an unexpected response of monocytes to Slit3 and add insights into the possible role of Slit proteins during inflammatory cell recruitment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monocitos
/
Movimiento Celular
/
Células Endoteliales
/
Proteínas de la Membrana
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Estados Unidos