title: Blood leukocytes and macrophages of various phenotypes have distinct abilities to form podosomes and to migrate in 3D environments.
abstract: Leukocytes migrate through most tissues in the body, a process which takes place in 3D environments. We have previously shown that macrophages use the amoeboid migration mode in porous matrices such as fibrillar collagen I and the mesenchymal mode involving podosomes and matrix proteolysis in dense matrices such as Matrigel. Whether such a plasticity may apply to other leukocytes and to all subsets of macrophages is unknown. Here, we therefore provide a comparative analysis of the in vitro 3D migration modes adopted by primary human leukocytes. Blood-derived monocytes, neutrophils and T lymphocytes were found to use the amoeboid mode in a porous fibrillar collagen I matrix but were unable to infiltrate dense Matrigel and to form podosomes. M2-polarized macrophages and elicited peritoneal macrophages formed podosome rosettes, degraded the ECM and infiltrated both matrices. In contrast, M1 macrophages were motionless in 2D and 3D environments, whilst resident macrophages, devoid of podosomes, were only able to use the amoeboid mode. Thus, we conclude that whereas all leukocytes use the amoeboid mode to migrate through porous matrices, it is only certain macrophages that can adopt the mesenchymal mode that permits migration through dense matrices. Interestingly, the acquisition of mesenchymal migration capacity by macrophages correlates with the presence of podosomes and with their capacity to organize those as rosettes, which appears to be modulated by their differentiation and polarization states. As a perspective, specific control of the mesenchymal migration would be a potential target for therapeutic approaches aiming at decreasing macrophage tissue infiltration.
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Cougoule
authors.forename: Emeline
authors.initials: E
authors.lastname: Van Goethem
authors.forename: Véronique
authors.initials: V
authors.lastname: Le Cabec
authors.forename: Fanny
authors.initials: F
authors.lastname: Lafouresse
authors.forename: Loïc
authors.initials: L
authors.lastname: Dupré
authors.forename: Vikram
authors.initials: V
authors.lastname: Mehraj
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mège
authors.forename: Claire
authors.initials: C
authors.lastname: Lastrucci
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maridonneau-Parini
mesh_terms: D002465:Cell Movement; D022081:Cell Surface Extensions / Q000502:physiology* / Q000648:ultrastructure; D003094:Collagen; D024042:Collagen Type I / Q000737:chemistry; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D007797:Laminin; D007962:Leukocytes / Q000502:physiology* / Q000648:ultrastructure*; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure*; D008968:Molecular Conformation; D010641:Phenotype; D011509:Proteoglycans
chemical_list: D024042:Collagen Type I; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen