title: The CD200-CD200 receptor inhibitory axis controls arteriogenesis and local T lymphocyte influx.
abstract: The role of the CD200 ligand-CD200 receptor (CD200-CD200R) inhibitory axis is highly important in controlling myeloid cell function. Since the activation of myeloid cells is crucial in arteriogenesis, we hypothesized that disruption of the CD200-CD200R axis promotes arteriogenesis in a murine hindlimb ischemia model. Female Cd200-/- and wildtype (C57Bl/6J) mice underwent unilateral femoral artery ligation. Perfusion recovery was monitored over 7 days using Laser-Doppler analysis and was increased in Cd200-/- mice at day 3 and 7 after femoral artery ligation, compared to wildtype. Histology was performed on hindlimb muscles at baseline, day 3 and 7 to assess vessel geometry and number and inflammatory cell influx. Vessel geometry in non-ischemic muscles was larger, and vessel numbers in ischemic muscles were increased in Cd200-/- mice compared to wildtype. Furthermore, T lymphocyte influx was increased in Cd200-/- compared to wildtype. CD200R agonist treatment was performed in male C57Bl/6J mice to validate the role of the CD200-CD200R axis in arteriogenesis. CD200R agonist treatment after unilateral femoral artery ligation resulted in a significant decrease in vessel geometry, perfusion recovery and T lymphocyte influx at day 7 compared to isotype treatment. In this study, we show a causal role for the CD200-CD200R inhibitory axis in arteriogenesis in a murine hindlimb ischemia model. Lack of CD200R signaling is accompanied by increased T lymphocyte recruitment to the collateral vasculature and results in enlargement of preexisting collateral arteries.
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Pleunie
authors.initials: P
authors.lastname: van den Borne
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Tomasz P
authors.initials: TP
authors.lastname: Rygiel
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Ayla
authors.initials: A
authors.lastname: Hoogendoorn
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Geertje H A
authors.initials: GH
authors.lastname: Westerlaken
authors.affiliation: Bioceros BV, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory of Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001158:Arteries / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics; D003097:Collateral Circulation; D005260:Female; D007511:Ischemia / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D064446:Orexin Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C501103:Cd200r1 protein, mouse; D064446:Orexin Receptors; C042739:antigens, CD200