Tissue damage detection by osmotic surveillance
- Authors
- Enyedi, B., Kala, S., Nikolich-Zugich, T., and Niethammer, P.
- ID
- ZDB-PUB-130903-14
- Date
- 2013
- Source
- Nature cell biology 15(9): 1123-30 (Journal)
- Registered Authors
- Enyedi, Balázs, Niethammer, Philipp
- Keywords
- none
- MeSH Terms
-
- Immunity, Innate
- Animals
- Gene Expression Regulation
- Extracellular Fluid/immunology
- Extracellular Fluid/metabolism
- Zebrafish/immunology*
- Chemotaxis, Leukocyte/immunology*
- Cytosol/immunology
- Cytosol/metabolism
- Osmosis*
- Wounds and Injuries/immunology*
- Wounds and Injuries/pathology
- Signal Transduction
- Leukocytes/immunology*
- Leukocytes/pathology
- Osmolar Concentration
- Phospholipases A2, Cytosolic/genetics
- Phospholipases A2, Cytosolic/immunology
- Lasers
- Chemotactic Factors/immunology
- Chemotactic Factors/metabolism
- Extracellular Space/immunology
- Extracellular Space/metabolism
- Larva/immunology*
- Arachidonic Acids/immunology
- Arachidonic Acids/metabolism
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/immunology
- PubMed
- 23934216 Full text @ Nat. Cell Biol.
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.