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PMID:19494811

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Citation

Niethammer, P, Grabher, C, Look, AT and Mitchison, TJ (2009) A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 459:996-9

Abstract

Barrier structures (for example, epithelia around tissues and plasma membranes around cells) are required for internal homeostasis and protection from pathogens. Wound detection and healing represent a dormant morphogenetic program that can be rapidly executed to restore barrier integrity and tissue homeostasis. In animals, initial steps include recruitment of leukocytes to the site of injury across distances of hundreds of micrometres within minutes of wounding. The spatial signals that direct this immediate tissue response are unknown. Owing to their fast diffusion and versatile biological activities, reactive oxygen species, including hydrogen peroxide (H(2)O(2)), are interesting candidates for wound-to-leukocyte signalling. Here we probe the role of H(2)O(2) during the early events of wound responses in zebrafish larvae expressing a genetically encoded H(2)O(2) sensor. This reporter revealed a sustained rise in H(2)O(2) concentration at the wound margin, starting approximately 3 min after wounding and peaking at approximately 20 min, which extended approximately 100-200 microm into the tail-fin epithelium as a decreasing concentration gradient. Using pharmacological and genetic inhibition, we show that this gradient is created by dual oxidase (Duox), and that it is required for rapid recruitment of leukocytes to the wound. This is the first observation, to our knowledge, of a tissue-scale H(2)O(2) pattern, and the first evidence that H(2)O(2) signals to leukocytes in tissues, in addition to its known antiseptic role.

Links

PubMed PMC2803098 Online version:10.1038/nature08119

Keywords

Animals; Diffusion; Hydrogen Peroxide/metabolism; Larva/metabolism; Leukocytes/cytology; Leukocytes/physiology; NADPH Oxidase/metabolism; Wound Healing/physiology; Wounds and Injuries/enzymology; Wounds and Injuries/metabolism; Wounds and Injuries/pathology; Zebrafish/genetics; Zebrafish/metabolism; Zebrafish Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A0A2R8QJC5

involved_in

GO:0002523: leukocyte migration involved in inflammatory response

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:A0A2R8QJC5

involved_in

GO:0009611: response to wounding

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:A0A2R8QJC5

involved_in

GO:0050665: hydrogen peroxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:A0A2R8RLY1

involved_in

GO:0002523: leukocyte migration involved in inflammatory response

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:A0A2R8RLY1

involved_in

GO:0009611: response to wounding

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:A0A2R8RLY1

involved_in

GO:0050665: hydrogen peroxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:F1QVF2

involved_in

GO:0002523: leukocyte migration involved in inflammatory response

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:F1QVF2

involved_in

GO:0009611: response to wounding

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:F1QVF2

involved_in

GO:0050665: hydrogen peroxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:Q08JS2

involved_in

GO:0002523: leukocyte migration involved in inflammatory response

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:Q08JS2

involved_in

GO:0009611: response to wounding

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete

DANRE:Q08JS2

involved_in

GO:0050665: hydrogen peroxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-091117-1

P

Seeded From UniProt

complete


See also

References

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