The effect of HMGB1, a damage-associated molecular pattern molecule, on polymorphonuclear neutrophil migration depends on its concentration.

Content Provider	Semantic Scholar
Author	Berthelot, Florence Fattoum, Lakhdar Casulli, Sarah Gozlan, Joël Maréchal, Vincent Elbim, Carole
Copyright Year	2012
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.
Starting Page	41
Ending Page	58
Page Count	18
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://www.karger.com/Article/Pdf/328798
PubMed reference number	21860212v1
Alternate Webpage(s)	https://doi.org/10.1159/000328798
DOI	10.1159/000328798
Journal	Journal of innate immunity
Volume Number	4
Issue Number	1
Language	English
Access Restriction	Open
Subject Keyword	Alarmins Body tissue Chemotactic Factors Chemotaxis HMGB1 Protein How True Feel Alert Right Now Immune system Interleukin-8 Microgram per Liter Microorganism N-Formylmethionine Leucyl-Phenylalanine TLR4 protein, human Toll-like receptors neutrophil physical hard work receptor for advanced glycation endproducts
Content Type	Text
Resource Type	Article