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

Konstantin Stark; Annekathrin Eckart; Selgai Haidari; Anca Tirniceriu; Michael Lorenz; Marie-Luise von Brühl; Florian Gärtner; Alexander Georg Khandoga; Kyle R Legate; Robert Pless; Ingrid Hepper; Kirsten Lauber; Barbara Walzog; Steffen Massberg

doi:10.1038/ni.2477

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

Nat Immunol. 2013 Jan;14(1):41-51. doi: 10.1038/ni.2477. Epub 2012 Nov 25.

Authors

Konstantin Stark¹, Annekathrin Eckart, Selgai Haidari, Anca Tirniceriu, Michael Lorenz, Marie-Luise von Brühl, Florian Gärtner, Alexander Georg Khandoga, Kyle R Legate, Robert Pless, Ingrid Hepper, Kirsten Lauber, Barbara Walzog, Steffen Massberg

Affiliation

¹ Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität and Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.

PMID: 23179077
DOI: 10.1038/ni.2477

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Blocking / pharmacology
Arterioles / immunology
Capillaries / immunology
Cell Communication / drug effects
Cell Movement / drug effects
Cell Movement / immunology
Cells, Cultured
Humans
Immunity, Innate
Inflammation Mediators / metabolism
Intercellular Adhesion Molecule-1 / genetics
Intercellular Adhesion Molecule-1 / metabolism*
Intramolecular Oxidoreductases / genetics
Intramolecular Oxidoreductases / immunology
Intramolecular Oxidoreductases / metabolism*
Leukocytes / drug effects
Leukocytes / immunology*
Macrophage Migration-Inhibitory Factors / genetics
Macrophage Migration-Inhibitory Factors / immunology
Macrophage Migration-Inhibitory Factors / metabolism*
Neutrophil Activation / drug effects
Pericytes / immunology*
Receptors, Pattern Recognition / immunology*
Up-Regulation / drug effects
Venules / immunology

Substances

Antibodies, Blocking
Inflammation Mediators
Macrophage Migration-Inhibitory Factors
Receptors, Pattern Recognition
Intercellular Adhesion Molecule-1
Intramolecular Oxidoreductases
MIF protein, human