Sphingosine 1 phosphate induces the chemotaxis of human natural killer cells. Role for heterotrimeric G proteins and phosphoinositide 3 kinases.
Eur J Immunol
; 32(7): 1856-64, 2002 Jul.
Article
em En
| MEDLINE
| ID: mdl-12115604
ABSTRACT
We have examined the effect of sphingolipids on the chemotaxis of human natural killer (NK) cells. Messenger RNA for Edg-1, Edg-6 and Edg-8 but not Edg-3, are expressed in these cells. Sphingosine 1 phosphate (SPP), dihydro SPP (DHSPP) or the CC chemokine RANTES (CCL5), but not sphingosine induces the chemotaxis of these cells. Pertussis toxin inhibits the chemotaxis induced by these ligands. Permeabilization of NK cells with streptolysin O (SLO) and introduction of blocking antibodies to the heterotrimeric G proteins, showed that Galpha(i2), Galpha(s), Galpha(q/11) or Galpha(13) mediate the chemotaxis of SPP, whereas Galpha(i2), Galpha(o) or Galpha(q/11) mediate the chemotaxis of DHSPP. Galpha(i2), Galpha(o), Galpha(s), Galpha(q/11), Galpha(z) or Galpha(12 )mediates RANTES-induced NK cell chemotaxis. Further analysis showed that phosphoinositide 3 kinase (PI3K) inhibitors wortmannin and LY294002 inhibit NK cell chemotaxis induced by SPP, DHSPP or RANTES. Blocking antibody to PI3Kgamma inhibits the chemotaxis induced by the three ligands, whereas anti-PI3Kbeta was without effect. In contrast, SPP and DHSPP recruit PI3Kbeta isozyme into NK cell membranes, suggesting that although this isoform is not involved in chemotaxis, it is activated by these phospholipids.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Esfingosina
/
Lisofosfolipídeos
/
Células Matadoras Naturais
/
Fatores Quimiotáticos
/
Quimiotaxia de Leucócito
/
Fosfatidilinositol 3-Quinases
/
Proteínas Heterotriméricas de Ligação ao GTP
/
Proteínas I-kappa B
/
Receptores Acoplados a Proteínas G
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Noruega