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Nat Cell Biol. 2013 Sep;15(9):1123-30. doi: 10.1038/ncb2818. Epub 2013 Aug 11.

Tissue damage detection by osmotic surveillance.

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1
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

Abstract

How tissue damage is detected to induce inflammatory responses is unclear. Most studies have focused on damage signals released by cell breakage and necrosis. Whether tissues use other cues in addition to cell lysis to detect that they are damaged is unknown. We find that osmolarity differences between interstitial fluid and the external environment mediate rapid leukocyte recruitment to sites of tissue damage in zebrafish by activating cytosolic phospholipase a2 (cPLA2) at injury sites. cPLA2 initiates the production of non-canonical arachidonate metabolites that mediate leukocyte chemotaxis through a 5-oxo-ETE receptor (OXE-R). Thus, tissues can detect damage through direct surveillance of barrier integrity, with cell swelling probably functioning as a pro-inflammatory intermediate in the process.

PMID:
23934216
PMCID:
PMC3826879
DOI:
10.1038/ncb2818
[Indexed for MEDLINE]
Free PMC Article
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