Macrophage movement in response to injury, inflammation and infection: Involvement of TRPM2 ion channels.

Abstract

Recent work suggests a novel mechanism by which macrophages seek out damaged tissues: they sense hydrogen peroxide released by tissue damage and navigate by travelling up the gradient of H2O2. What is the mechanism? H2O2 is known to activate a thermally sensitive ion channel, TRPM2, and an influx of calcium through this ion channel may “steer” a macrophage towards a site of tissue damage.  The project will use mRNA sequencing, bioinformatics and both in vitro and in vivo experiments to establish how macrophages detect hydrogen peroxide and how important this mechanism in navigating towards damaged tissue.

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References:
[1]

Knowles H, Heizer JW, Li Y, Chapman K, Ogden CA, Andreasen K, Shapland E, Kucera G, Mogan J, Humann J, Lenz LL, Morrison AD, Perraud AL. Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity against Listeria monocytogenes. Proc Natl Acad Sci U S A 2011;108:11578-11583.

[2]

Niethammer P, Grabher C, Look AT, Mitchison TJ. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 2009;459:996-999

[3]

Old EA, Nadkarni S, Grist J, Gentry C, Bevan S, Kim KW, Mogg AJ, Perretti M, Malcangio M. Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain. J Clin Invest 2014 (in press).

[4]

Zou J, Ainscough JF, Yang W, Sedo A, Yu SP, Mei ZZ, Sivaprasadarao A, Beech DJ, Jiang LH. A differential role of macrophage TRPM2 channels in Ca(2)(+) signaling and cell death in early responses to H(2)O(2). Am J Physiol Cell Physiol 2013;305:C61-C69.


Biological Areas:

Cell Biology
Immunology

BBSRC Area:

Animal disease, health and welfare