In vivo imaging reveals a pioneer wave of monocyte recruitment into mouse skin wounds

Mathieu P Rodero; Fabrice Licata; Lucie Poupel; Pauline Hamon; Kiarash Khosrotehrani; Christophe Combadiere; Alexandre Boissonnas

doi:10.1371/journal.pone.0108212

In vivo imaging reveals a pioneer wave of monocyte recruitment into mouse skin wounds

PLoS One. 2014 Oct 1;9(10):e108212. doi: 10.1371/journal.pone.0108212. eCollection 2014.

Authors

Mathieu P Rodero¹, Fabrice Licata¹, Lucie Poupel¹, Pauline Hamon¹, Kiarash Khosrotehrani², Christophe Combadiere¹, Alexandre Boissonnas¹

Affiliations

¹ Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), 91 Bd de l'hôpital, Paris, France; INSERM, U1135, CIMI, 91 Bd de l'hôpital, Paris, France; CNRS, ERL, CIMI, 91 Bd de l'hôpital, Paris, France.
² The University of Queensland, UQ Centre for Clinical Research, Brisbane, QLD, Australia; The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Woolloongabba, QLD, Australia.

Abstract

The cells of the mononuclear phagocyte system are essential for the correct healing of adult skin wounds, but their specific functions remain ill-defined. The absence of granulation tissue immediately after skin injury makes it challenging to study the role of mononuclear phagocytes at the initiation of this inflammatory stage. To study their recruitment and migratory behavior within the wound bed, we developed a new model for real-time in vivo imaging of the wound, using transgenic mice that express green and cyan fluorescent proteins and specifically target monocytes. Within hours after the scalp injury, monocytes invaded the wound bed. The complete abrogation of this infiltration in monocyte-deficient CCR2(-/-) mice argues for the involvement of classical monocytes in this process. Monocyte infiltration unexpectedly occurred as early as neutrophil recruitment did and resulted from active release from the bloodstream toward the matrix through microhemorrhages rather than transendothelial migration. Monocytes randomly scouted around the wound bed, progressively slowed down, and stopped. Our approach identified and characterized a rapid and earlier than expected wave of monocyte infiltration and provides a novel framework for investigating the role of these cells during early stages of wound healing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chemotaxis, Leukocyte
Disease Models, Animal
Mice
Mice, Knockout
Microscopy, Fluorescence, Multiphoton
Monocytes / immunology*
Monocytes / pathology*
Neutrophil Infiltration
Skin / immunology*
Skin / pathology*
Wound Healing*
Wounds and Injuries / immunology*
Wounds and Injuries / pathology*

Grants and funding

This work was supported by grants from Inserm, UPMC emergence, European Grant ENDOSTEM (FP7 #241440), ANR Emergence “I-CKAIRE” (ANR-12-EMMA-0050). KK is supported by an NHMRC career development fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.