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PTEN functions to 'prioritize' chemotactic cues and prevent 'distraction' in migrating neutrophils.

Abstract：

:Neutrophils encounter and 'prioritize' many chemoattractants in their pursuit of bacteria. Here we tested the possibility that the phosphatase PTEN is responsible for the prioritization of chemoattractants. Neutrophils induced chemotaxis by two separate pathways, the phosphatidylinositol-3-OH kinase (PI(3)K) phosphatase and tensin homolog (PTEN) pathway, and the p38 mitogen-activated protein kinase pathway, with the p38 pathway dominating over the PI(3)K pathway. Pten(-/-) neutrophils could not prioritize chemoattractants and were 'distracted' by chemokines when moving toward bacterial chemoattractants. In opposing gradients, PTEN became distributed throughout the cell circumference, which inhibited all PI(3)K activity, thus permitting 'preferential' migration toward bacterial products via phospholipase A(2) and p38. Such prioritization was defective in Pten(-/-) neutrophils, which resulted in defective bacterial clearance in vivo. Our data identify a PTEN-dependent mechanism in neutrophils to prioritize, 'triage' and integrate responses to multiple chemotactic cues.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Heit B,Robbins SM,Downey CM,Guan Z,Colarusso P,Miller BJ,Jirik FR,Kubes P

doi

10.1038/ni.1623

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

743-52

issue

7

eissn

1529-2908

issn

1529-2916

pii

ni.1623

journal_volume

9

pub_type

杂志文章

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