title: Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and 'instruct' them with pattern-recognition and motility programs.
abstract: Coordinated navigation within tissues is essential for cells of the innate immune system to reach the sites of inflammatory processes, but the signals involved are incompletely understood. Here we demonstrate that NG2(+) pericytes controlled the pattern and efficacy of the interstitial migration of leukocytes in vivo. In response to inflammatory mediators, pericytes upregulated expression of the adhesion molecule ICAM-1 and released the chemoattractant MIF. Arteriolar and capillary pericytes attracted and interacted with myeloid leukocytes after extravasating from postcapillary venules, 'instructing' them with pattern-recognition and motility programs. Inhibition of MIF neutralized the migratory cues provided to myeloid leukocytes by NG2(+) pericytes. Hence, our results identify a previously unknown role for NG2(+) pericytes as an active component of innate immune responses, which supports the immunosurveillance and effector function of extravasated neutrophils and macrophages.
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität and Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Stark
authors.forename: Annekathrin
authors.initials: A
authors.lastname: Eckart
authors.forename: Selgai
authors.initials: S
authors.lastname: Haidari
authors.forename: Anca
authors.initials: A
authors.lastname: Tirniceriu
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: von Brühl
authors.forename: Florian
authors.initials: F
authors.lastname: Gärtner
authors.forename: Alexander Georg
authors.initials: AG
authors.lastname: Khandoga
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Legate
authors.forename: Robert
authors.initials: R
authors.lastname: Pless
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hepper
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Barbara
authors.initials: B
authors.lastname: Walzog
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D001160:Arterioles / Q000276:immunology; D002196:Capillaries / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018375:Neutrophil Activation / Q000187:drug effects; D020286:Pericytes / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects; D014699:Venules / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D051192:Receptors, Pattern Recognition; D018799:Intercellular Adhesion Molecule-1; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human