Getting to the Scene

Sci. Signal.  23 Jun 2009:
Vol. 2, Issue 76, pp. ec209
DOI: 10.1126/scisignal.276ec209

In one of the earliest responses to injury, leukocytes travel hundreds of μms to reach wounds within minutes of injury. However, the initial signals that alert them and direct their migration remain unclear (see Martin and Feng). Niethammer et al. used HyPer, a genetically encoded fluorescent sensor for hydrogen peroxide (H2O2), to identify an extracellular H2O2 gradient as playing a critical role in injury-dependent leukocyte recruitment in zebrafish larvae. Tailfin injury led to a rapid increase in H2O2, which peaked by about 20 minutes after the injury, forming a gradient that extended about 100 to 200 μm from the injury site. The H2O2 signal preceded leukocyte recruitment, with arrival of leukocytes at the wound taking an average of about 17 minutes. Pharmacological analysis indicated that the H2O2 signal—and leukocyte recruitment—depended on activity of enzymes in the NADPH oxidase (Nox) family. Global disruption of pre-mRNA splicing of various Nox enzymes with antisense morpholino oligonucleotides, in combination with semiquantitative polymerase chain reaction, specifically implicated dual oxidase (Duox) in the response. Thus, the authors conclude that H2O2 represents a critical signal for recruiting leukocytes to injury sites. Precisely how wounding activates Duox—and how H2O2 elicits leukocyte migration—remains to be determined.

P. Niethammer, C. Grabher, A. T. Look, T. J. Mitchison, A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 459, 996–999 (2009). [PubMed]

P. Martin, Y. Feng, Wound healing in zebrafish. Nature 459, 921–923 (2009). [PubMed]