Journal of Leukocyte Biology
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(Journal of Leukocyte Biology. 2007;81:263-271.)
© 2007 by Society for Leukocyte Biology

Birth and life of tissue macrophages and their migration in embryogenesis and inflammation in medaka

Clemens Grabher*,1,2, Adam Cliffe*,1, Kota Miura{dagger},{ddagger}, Joel Hayflick{ddagger}, Rainer Pepperkok{dagger}, Pernille Rørth* and Joachim Wittbrodt*,2

* Developmental Biology Unit, and
{dagger} Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany; and
{ddagger} ICOS Corporation, Bothell, Washington, USA

2Correspondence: C.G., Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA. E-mail: clemens_grabher{at}dfci.harvard.edu; J.W., Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhoftsr. 1, Heidelberg 69117, Germany. E-mail: wittbrodt{at}embl.de

Macrophages detecting and migrating toward sites of injury and infection represent one of the first steps in an immune response. Here we directly image macrophage birth and migration in vivo in transgenic medaka fish. Macrophages are born as frequently dividing, immotile cells with spherical morphology that differentiate into flat, highly motile cells. They retain mitotic activity while spreading over the entire body. Cells follow restricted paths not only in directed migration, but also during patrolling. Along those paths the macrophages rapidly patrol the tissue and respond to wounding and bacterial infection from long distances. Upon injury they increase their speed and migratory persistence. Specifically targeting PI3-kinase isoforms efficiently blocks the wounding response and results in a distinct inhibition of cell motility and chemotaxis. Our study provides in situ insights into the properties of immature and migratory macrophages and presents a unique model to further test modulating compounds in vivo.

Key Words: Macrophage • cell migration • medaka • PI3K • inflammation




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