PT  - JOURNAL ARTICLE
AU  - Jana Travnickova
AU  - Sandra Nhim
AU  - Naoill Abdellaoui
AU  - Farida Djouad
AU  - Maï Nguyen-Chi
AU  - Andrea Parmeggiani
AU  - Karima Kissa
TI  - Macrophage plasticity is Rac signalling and MMP9 dependant
AID  - 10.1101/614388
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 614388
4099  - http://biorxiv.org/content/early/2019/04/19/614388.short
4100  - http://biorxiv.org/content/early/2019/04/19/614388.full
AB  - In vitro, depending on extracellular matrix (ECM) architecture, macrophages migrate either in amoeboid or mesenchymal mode; while the first is a general trait of leukocytes, the latter is associated with tissue remodelling via Matrix Metalloproteinases (MMPs). To assess whether these stereotyped migrations could be also observed in a physiological context, we used the zebrafish embryo and monitored macrophage morphology, behaviour and capacity to mobilisation haematopoietic stem/progenitor cells (HSPCs), as a final functional readout. Morphometric analysis identified 4 different cell shapes. Live imaging revealed that macrophages successively adopt all four shapes as they migrate through ECM. Treatment with inhibitors of MMPs or Rac GTPase to abolish mesenchymal migration, suppresses both ECM degradation and HSPC mobilisation while differently affecting macrophage behaviour. This study depicts real time macrophage behaviour in a physiological context and reveals extreme reactivity of these cells constantly adapting and switching migratory shapes to achieve HSPCs proper mobilisation.AGMAorta-Gonad-MesonephrosHSPCHaematopoietic stem and progenitor cellsMMPMatrix metalloproteinasesTAMTumour associated macrophages