title: Differentiation to the CCR2+ inflammatory phenotype in vivo is a constitutive, time-limited property of blood monocytes and is independent of local inflammatory mediators.
abstract: It is proposed that CCR2+ monocytes are specifically recruited to inflammatory sites, whereas CCR2- monocytes are recruited to normal tissue to become resident macrophages. Whether these subsets represent separate lineages, how differential trafficking is regulated and whether monocytes undergo further differentiation is uncertain. Using a mouse model of autoimmune uveoretinitis we examined monocyte trafficking to the inflamed retina in vivo. We show that bone marrow-derived CD11b+ F4/80- monocytes require 24 to 48 h within the circulation and lymphoid system before acquiring the CCR2+ phenotype and trafficking to the inflamed retina is enabled. This phenotype, and the capacity to traffic were lost by 72 h. Monocyte CCR2 expression followed a similar time course in normal mice indicating that differentiation to an inflammatory phenotype is a constitutive, time-limited property, independent of local inflammatory mediators. Phenotypic analysis of adoptively transferred cells indicated that circulating inflammatory monocytes also differentiate into CD11c+ and B220+ dendritic cells and F4/80+ tissue macrophages in vivo. Our data supports the hypothesis of continuous extravasation and progressive differentiation over time of inflammatory monocytes in the circulation rather than replication within the actively inflamed tissue, and supports the concept of myeloid dendritic cell differentiation from trafficking monocytes under physiological conditions in vivo.
authors.affiliation: Department of Ophthalmology, Institute of Medical Science, University of Aberdeen, UK. h.xu@abdn.ac.uk
authors.forename: Heping
authors.initials: H
authors.lastname: Xu
authors.forename: Ayyakkannu
authors.initials: A
authors.lastname: Manivannan
authors.forename: Rosemary
authors.initials: R
authors.lastname: Dawson
authors.forename: Isabel J
authors.initials: IJ
authors.lastname: Crane
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Peter
authors.initials: P
authors.lastname: Sharp
authors.forename: Janet
authors.initials: J
authors.lastname: Liversidge
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000276:immunology / Q000473:pathology; D012173:Retinitis / Q000276:immunology / Q000473:pathology; D014605:Uveitis / Q000276:immunology / Q000473:pathology
chemical_list: D039521:CD11c Antigen; C515335:Ccr2 protein, mouse; D018836:Inflammation Mediators; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens