Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis.
Proc Natl Acad Sci U S A
; 99(6): 3603-8, 2002 Mar 19.
Article
em En
| MEDLINE
| ID: mdl-11904423
ABSTRACT
Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase gamma (PI3K)gamma(-/-) neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kgamma(-/-) neutrophils failed to translocate up the chemotactic gradient. A partial reduction in cell motility and abnormal morphologies were also observed. In the wild-type neutrophils, the pleckstrin homology domain-containing protein kinase B (AKT) and F-actin colocalize to the leading edge of polarized neutrophils oriented toward the gradient, which was not observed in PI3Kgamma(-/-) neutrophils. In PI3Kgamma(-/-) neutrophils, AKT staining consistently failed to perfectly overlap with the F-actin. This failure was observed as an F-actin-filled region of 2.3 +/- 0.5 microm between AKT and the cell membrane. These data suggest that PI3Kgamma regulates neutrophil chemotaxis primarily by controlling the direction of cell migration and the intracellular colocalization of AKT and F-actin to the leading edge.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quimiotaxia de Leucócito
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Proteínas Serina-Treonina Quinases
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Fosfatidilinositol 3-Quinases
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Isoenzimas
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N-Formilmetionina Leucil-Fenilalanina
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Neutrófilos
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article