Article abstract

Nature Immunology 9, 743 - 752 (2008)
Published online: 8 June 2008 | Corrected online: 21 July 2008 | doi:10.1038/ni.1623

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

Bryan Heit1, Stephen M Robbins2,3, Charlene M Downey4, Zhiwen Guan1, Pina Colarusso1, B Joan Miller4, Frank R Jirik4 & Paul Kubes1

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 A2 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.

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  1. Immunology Research Group, Institute of Infection and Immunity, University of Calgary, Calgary T2N 4N1, Canada.
  2. Department of Oncology, University of Calgary, Calgary T2N 4N1, Canada.
  3. Department of Biochemistry and Molecular Biology, University of Calgary, Calgary T2N 4N1, Canada.
  4. The McCaig Institute for Bone and Joint Health, University of Calgary, Calgary T2N 4N1, Canada.

Correspondence to: Paul Kubes1 e-mail: pkubes@ucalgary.ca

* In the version of this article initially published, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) is incorrectly identified as phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2). The error has been corrected in the HTML and PDF versions of the article.

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