Macrophage morphological plasticity and migration is Rac signalling and MMP9 dependant

Abstract

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 mobilise 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.

Vitreoretinal Interface Cells Correlate In Vivo With Uveitis Activity and Decrease With Anti-Inflammatory Treatment

“…In our study, VRICs showed an ameboid movement pattern on the retinal surface and along blood vessels. 26 This is aligned with their critical immune patrolling and response functions, as well as chasing chemotactic signals and revealing an increase in shape plasticity, which confirmed the outcome of previous studies performed in vitro. 27 …”

“…The x - and y -planes are the only ones explored in our manuscript, as we currently have no information on the z -plane that might identify VRICs through the neuroretinal layers. 26 Although it might be perceived as marginal, this biodynamic aspect may significantly contribute to defining the macrophage migration dynamic, clarifying whether they adopt a prevalent ameboid or mesenchymal migratory pattern or behave differently depending on the plane that they interact with. In addition, the potential migration toward the retinal pigment epithelium might lead to further hypotheses on the interplay of VRICs with the choroidal immune compartment.…”

A macrophage subpopulation promotes airineme-mediated intercellular communication in a Matrix Metalloproteinase-9 dependent manner

“…Matrix Metalloproteinases (MMPs) are a critical component of macrophage migration. Among many MMPs, MMP9 has been suggested to be required for macrophage migration and phagocytosis (Gong et al, 2008; Travnickova et al, 2021). Therefore, we hypothesized that the differential MMP9 requirement governs migratory behavior between amoeboid/metaphocytes and dendritic macrophages in zebrafish skin.…”

“…Macrophages can infiltrate most tissues and migrate between cells in vivo by degrading extracellular matrix (ECM) with extracellular proteinases such as matrix metalloproteinases (MMPs), cathepsins, and urokinase-type plasminogen activator (Verollet et al, 2011). A few studies have shown that MMP9 activity is critical in macrophage migration in mice and zebrafish (Gong et al, 2008; Travnickova et al, 2021).…”

Mechanosensing in macrophages and dendritic cells in steady-state and disease

“…Murine RAW264.7 macrophages or primary human alveolar macrophages cultured on less rigid substrates display a more rounded shape compared to those cultured on a more rigid substrate ( Patel et al, 2012 ). Such morphological adaptations may be highly relevant in the movement of macrophages, which adopt different migration modes in response to environmental constraints ( Van Goethem et al, 2010 ; Vérollet et al, 2011 ; Travnickova et al, 2021 ).…”