Tissue damage detection by osmotic surveillance.
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.
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Balázs
B
Enyedi
Snigdha
S
Kala
Tijana
T
Nikolich-Zugich
Philipp
P
Niethammer
D000818:Animals; D001095:Arachidonic Acids / Q000276:immunology / Q000378:metabolism; D002630:Chemotactic Factors / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D045604:Extracellular Fluid / Q000276:immunology / Q000378:metabolism; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007814:Larva / Q000276:immunology*; D007834:Lasers; D007962:Leukocytes / Q000276:immunology* / Q000473:pathology; D009994:Osmolar Concentration; D009995:Osmosis; D054510:Phospholipases A2, Cytosolic / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014947:Wounds and Injuries / Q000276:immunology* / Q000473:pathology; D015027:Zebrafish / Q000276:immunology*
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D011956:Receptors, Cell Surface; D054510:Phospholipases A2, Cytosolic