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PMID: 23179077 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and 'instruct' them with pattern-recognition and motility programs.

Nature immunology ·Vol. 14 ·No. 1 ·2013-01-00 ·Pages 41-51

Stark K, Eckart A, Haidari S, Tirniceriu A, Lorenz M, von Brühl ML, Gärtner F, Khandoga AG, Legate KR, Pless R, Hepper I, Lauber K, Walzog B, Massberg S

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.

MeSH Terms
Antibodies, Blocking/pharmacology Arterioles/immunology Capillaries/immunology Cell Communication/drug effects Cell Movement/drug effects,immunology Cells, Cultured Humans Immunity, Innate Inflammation Mediators/metabolism Intercellular Adhesion Molecule-1/genetics,metabolism Intramolecular Oxidoreductases/genetics,immunology,metabolism Leukocytes/drug effects,immunology Macrophage Migration-Inhibitory Factors/genetics,immunology,metabolism Neutrophil Activation/drug effects Pericytes/immunology Receptors, Pattern Recognition/immunology Up-Regulation/drug effects Venules/immunology
Chemicals
Antibodies, Blocking Inflammation Mediators Macrophage Migration-Inhibitory Factors Receptors, Pattern Recognition Intercellular Adhesion Molecule-1 Intramolecular Oxidoreductases MIF protein, human
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Stark Konstantin
Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität and Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
Eckart Annekathrin
Haidari Selgai
Tirniceriu Anca
Lorenz Michael
von Brühl Marie-Luise
Gärtner Florian
Khandoga Alexander Georg
Legate Kyle R
Pless Robert
Hepper Ingrid
Lauber Kirsten
Walzog Barbara
Massberg Steffen
References (50)
50 references, click to expand
  1. Random versus directionally persistent cell migration.
    Nat Rev Mol Cell Biol. 2009 Aug;10(8):538-49 PMID: 19603038
  2. The neutrophil in vascular inflammation.
    Nat Med. 2011 Nov 07;17(11):1381-90 PMID: 22064428
  3. Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes.
    Endocrinology. 2005 Jul;146(7):2942-51 PMID: 15790730
  4. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases.
    Nature. 2004 Jan 8;427(6970):154-9 PMID: 14712275
  5. Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events.
    J Invest Dermatol. 2011 Oct;131(10):2058-68 PMID: 21697893
  6. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment.
    Nat Med. 2007 May;13(5):587-96 PMID: 17435771
  7. Intravascular danger signals guide neutrophils to sites of sterile inflammation.
    Science. 2010 Oct 15;330(6002):362-6 PMID: 20947763
  8. Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation.
    J Mol Med (Berl). 2011 Nov;89(11):1079-88 PMID: 21751029
  9. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia.
    Nat Med. 2010 Apr;16(4):420-8 PMID: 20364125
  10. Differential arterial/venous expression of NG2 proteoglycan in perivascular cells along microvessels: identifying a venule-specific phenotype.
    Microcirculation. 2005 Mar;12(2):151-60 PMID: 15824037
  11. Pericytes regulate the blood-brain barrier.
    Nature. 2010 Nov 25;468(7323):557-61 PMID: 20944627
  12. Differential immune cell dynamics in the CNS cause CD4+ T cell compartmentalization.
    Brain. 2009 May;132(Pt 5):1247-58 PMID: 19179377
  13. Neural crest-derived pericytes promote egress of mature thymocytes at the corticomedullary junction.
    Science. 2010 May 28;328(5982):1129-35 PMID: 20413455
  14. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo.
    Nat Immunol. 2011 Jun 26;12(8):761-9 PMID: 21706006
  15. Multistep navigation and the combinatorial control of leukocyte chemotaxis.
    J Cell Biol. 1997 Dec 1;139(5):1349-60 PMID: 9382879
  16. Breaching multiple barriers: leukocyte motility through venular walls and the interstitium.
    Nat Rev Mol Cell Biol. 2010 May;11(5):366-78 PMID: 20414258
  17. Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules.
    J Immunol. 2010 Jul 15;185(2):1238-47 PMID: 20554956
  18. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes.
    Immunity. 2006 Dec;25(6):989-1001 PMID: 17112751
  19. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells.
    Nat Immunol. 2007 Nov;8(11):1255-65 PMID: 17893676
  20. Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells.
    Apoptosis. 2010 Sep;15(9):1007-28 PMID: 20157780
  21. Intravital microscopy: visualizing immunity in context.
    Immunity. 2004 Sep;21(3):315-29 PMID: 15357943
  22. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis.
    Nat Immunol. 2009 Mar;10(3):241-7 PMID: 19221555
  23. NG2 cells generate both oligodendrocytes and gray matter astrocytes.
    Development. 2008 Jan;135(1):145-57 PMID: 18045844
  24. LTB4 is a signal-relay molecule during neutrophil chemotaxis.
    Dev Cell. 2012 May 15;22(5):1079-91 PMID: 22542839
  25. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises.
    Dev Cell. 2011 Aug 16;21(2):193-215 PMID: 21839917
  26. Macrophage migration inhibitory factor regulates neutrophil chemotactic responses in inflammatory arthritis in mice.
    Arthritis Rheum. 2011 Apr;63(4):960-70 PMID: 21452319
  27. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node.
    Science. 2002 Jun 7;296(5574):1869-73 PMID: 12016203
  28. Interstitial leukocyte migration and immune function.
    Nat Immunol. 2008 Sep;9(9):960-9 PMID: 18711433
  29. T lymphocyte adhesion to human brain pericytes is mediated via very late antigen-4/vascular cell adhesion molecule-1 interactions.
    J Immunol. 1995 Jun 1;154(11):5876-84 PMID: 7538536
  30. Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway.
    FASEB J. 2003 Dec;17(15):2221-30 PMID: 14656984
  31. Reduced leukocyte-endothelial cell interactions in the inflamed microcirculation of macrophage migration inhibitory factor-deficient mice.
    Arthritis Rheum. 2004 Sep;50(9):3023-34 PMID: 15457472
  32. MIF as a disease target: ISO-1 as a proof-of-concept therapeutic.
    Future Med Chem. 2011 Jan;3(1):45-63 PMID: 21428825
  33. Immune cell migration in inflammation: present and future therapeutic targets.
    Nat Immunol. 2005 Dec;6(12):1182-90 PMID: 16369557
  34. A proinflammatory cytokine inhibits p53 tumor suppressor activity.
    J Exp Med. 1999 Nov 15;190(10):1375-82 PMID: 10562313
  35. Endothelial/pericyte interactions.
    Circ Res. 2005 Sep 16;97(6):512-23 PMID: 16166562
  36. Sterile inflammation: sensing and reacting to damage.
    Nat Rev Immunol. 2010 Dec;10(12):826-37 PMID: 21088683
  37. Intravital multiphoton imaging of immune responses in the mouse ear skin.
    Nat Protoc. 2012 Jan 12;7(2):221-34 PMID: 22240584
  38. Lipopolysaccharide activation of pericyte's Toll-like receptor-4 regulates co-culture permeability.
    Am J Surg. 2007 Jun;193(6):730-5 PMID: 17512285
  39. Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells.
    Immunity. 2010 May 28;32(5):703-13 PMID: 20471289
  40. Getting to the site of inflammation: the leukocyte adhesion cascade updated.
    Nat Rev Immunol. 2007 Sep;7(9):678-89 PMID: 17717539
  41. A small-molecule macrophage migration inhibitory factor antagonist protects against glomerulonephritis in lupus-prone NZB/NZW F1 and MRL/lpr mice.
    J Immunol. 2011 Jan 1;186(1):527-38 PMID: 21106847
  42. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    Methods. 2001 Dec;25(4):402-8 PMID: 11846609
  43. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo.
    J Exp Med. 2012 Jun 4;209(6):1219-34 PMID: 22615129
  44. How dying cells alert the immune system to danger.
    Nat Rev Immunol. 2008 Apr;8(4):279-89 PMID: 18340345
  45. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion.
    Mol Cell Biol. 2000 Jun;20(11):4106-14 PMID: 10805752
  46. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior.
    Science. 2007 Aug 3;317(5838):666-70 PMID: 17673663
  47. Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes.
    J Neurosci Res. 1999 Mar 1;55(5):578-87 PMID: 10082080
  48. Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages.
    Blood. 2000 Jul 15;96(2):719-26 PMID: 10887140
  49. Circulating mitochondrial DAMPs cause inflammatory responses to injury.
    Nature. 2010 Mar 4;464(7285):104-7 PMID: 20203610
  50. In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation.
    Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18073-8 PMID: 20923880
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2477
Published
2013-01-00
Epub
2012-00-25
Pages
41-51
Language
English
Region
United States
NLM ID
100941354
Subset
IM
Corrections
CommentIn
PMID: 23222503
CommentIn
PMID: 23238752
External Links
PubMed source DOI: 10.1038/ni.2477 View journal details
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