Monocyte behaviour and tissue transglutaminase expression during experimental autoimmune encephalomyelitis in transgenic CX3CR1gfp/gfpmice.
Leukocyte infiltration into the central nervous system (CNS) is a key pathological feature in multiple sclerosis (MS) and the MS animal model experimental autoimmune encephalomyelitis (EAE). Recently, preventing leukocyte influx into the CNS of MS patients is the main target of MS therapies and insight into cell behaviour in the circulation is needed for further elucidation of such therapies. In this study, we aimed at in vivo visualization of monocytes in a time-dependent manner during EAE. Using intravital two-photon microscopy (IVM), we imaged CX3CR1gfp/gfpmice during EAE, visualizing CX3CR1-GFP+monocytes and their dynamics in the spinal cord vasculature. Our observations showed that intraluminal crawling of CX3CR1-GFP+monocytes increased even before the clinical onset of EAE due to immunization of the animals. Furthermore, intraluminal crawling remained elevated during ongoing clinical disease. Besides, the displacement of these cells was larger during the peak of EAE compared to the control animals. In addition, we showed that the enzyme tissue transglutaminase (TG2), which is present in CNS-infiltrated cells in MS patients, is likewise found in CX3CR1-GFP+monocytes in the spinal cord lesions and at the luminal side of the vasculature during EAE. It might thereby contribute to adhesion and crawling of monocytes, facilitating extravasation into the CNS. Thus, we put forward that interference with monocyte adhesion, by e.g. inhibition of TG2, should be applied at a very early stage of EAE and possibly MS, to effectively combat subsequent pathology.
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
Navina L
NL
Chrobok
European Research Center for Medical Imaging, Developmental Biology Institute of Marseille, Aix Marseille Université, Campus de la Timone, Marseille, France.
Alexandre
A
Jaouen
European Research Center for Medical Imaging, Developmental Biology Institute of Marseille, Aix Marseille Université, Campus de la Timone, Marseille, France.|Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada.
Keith K
KK
Fenrich
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
John G J M
JG
Bol
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
Micha M M
MM
Wilhelmus
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
Benjamin
B
Drukarch
European Research Center for Medical Imaging, Developmental Biology Institute of Marseille, Aix Marseille Université, Campus de la Timone, Marseille, France.
Franck
F
Debarbieux
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands. amw.vandam@vumc.nl.
Anne-Marie
0000-0003-4191-3941
AM
van Dam
D000818:Animals; D000073883:CX3C Chemokine Receptor 1 / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion; D002465:Cell Movement; D058948:Cell Tracking; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D057054:Molecular Imaging / Q000379:methods; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013116:Spinal Cord / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology*
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
Cell crawling; Immunohistochemistry; Intravital microscopy; Multiple sclerosis