Open AccessLipid peroxidation regulates long-range wound detection through 5-lipoxygenase in zebrafish
Author(s) -
Anushka Katikaneni,
Mark Jelcic,
Gary F. Gerlach,
Yong Ma,
Michael Overholtzer,
Philipp Niethammer
Publication year - 2020
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-020-0564-2
Subject(s) - arachidonic acid , lipoxygenase , lipid peroxidation , microbiology and biotechnology , hydrogen peroxide , biochemistry , reactive oxygen species , chemotaxis , chemistry , zebrafish , nadph oxidase , biology , oxidative stress , enzyme , receptor , gene
Rapid wound detection by distant leukocytes is essential for antimicrobial defence and post-infection survival 1 . The reactive oxygen species hydrogen peroxide and the polyunsaturated fatty acid arachidonic acid are among the earliest known mediators of this process 2-4 . It is unknown whether or how these highly conserved cues collaborate to achieve wound detection over distances of several hundreds of micrometres within a few minutes. To investigate this, we locally applied arachidonic acid and skin-permeable peroxide by micropipette perfusion to unwounded zebrafish tail fins. As in wounds, arachidonic acid rapidly attracted leukocytes through dual oxidase (Duox) and 5-lipoxygenase (Alox5a). Peroxide promoted chemotaxis to arachidonic acid without being chemotactic on its own. Intravital biosensor imaging showed that wound peroxide and arachidonic acid converged on half-millimetre-long lipid peroxidation gradients that promoted leukocyte attraction. Our data suggest that lipid peroxidation functions as a spatial redox relay that enables long-range detection of early wound cues by immune cells, outlining a beneficial role for this otherwise toxic process.