Journal of Innate Immunity

Research Article

Free Access

The Effect of HMGB1, a Damage-Associated Molecular Pattern Molecule, on Polymorphonuclear Neutrophil Migration Depends on Its Concentration

Berthelot F. · Fattoum L. · Casulli S. · Gozlan J. · Maréchal V. · Elbim C.

Author affiliations

Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMR S 872 et Université Paris Descartes, UMR S 872, INSERM, Paris, France

Corresponding Author

Prof. Carole Elbim

Centre de Recherche des Cordeliers

Université Pierre et Marie Curie – Paris 6, UMR S 872

15 rue de l’École de Médecine, FR–75006 Paris (France)

Tel. +33 1 44 27 71 09, E-Mail carole.elbim@upmc.fr

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J Innate Immun 2012;4:41–58

Abstract

Polymorphonuclear neutrophils (PMN) play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in case of excessive or misdirected responses. Release of the alarmin high-mobility group box 1 (HMGB1) by cells that die at an inflammatory site may act as an alert signal for the immune system. We studied the effect of HMGB1 on human PMN migration, using whole-blood samples to avoid cell activation associated with isolation procedures. HMGB1 50–100 ng/ml reduced baseline PMN migration as well as formyl-methionyl-leucyl-phenylalanine- and IL-8-induced PMN chemotaxis. This inhibitory effect was mediated by the RAGE receptor. In contrast, a higher HMGB1 concentration (5,000 ng/ml) had a chemoattractant effect on PMN through IL-8 production. This effect required the engagement of Toll-like receptors 2 and 4 in addition to the RAGE receptor. The A box component of HMGB1, which antagonizes the endogenous protein, reduced chemotaxis and also strongly inhibited the enhancement of PMN migration observed with the highest HMGB1 concentration. In contrast, the B box, reported to be the active form of HMGB1, exerted a chemoattractant effect. These results strongly point to a key regulatory role of HMGB1 in PMN recruitment to inflammatory tissues. The A box component could potentially serve to inhibit inappropriate PMN recruitment during chronic inflammatory disorders associated with excessive HMGB1 release.

© 2011 S. Karger AG, Basel




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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: November 04, 2010
Accepted: April 18, 2011
Published online: August 19, 2011
Issue release date: December 2011

Number of Print Pages: 18
Number of Figures: 7
Number of Tables: 0

ISSN: 1662-811X (Print)
eISSN: 1662-8128 (Online)

For additional information: https://www.karger.com/JIN


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