HMGB1 AS A MAJOR “ALARMIN”
Signaling cellular stress or infection to the immune system is a critical obligation for multicellular organisms. Due to their microbial origin, a subset of these warning signals has been recognized as a coherent functional group called “pathogen-associated molecular pattern” or PAMPs.
These molecules alert the immune system following their recognition by toll-like receptors (TLRs) expressed at the surface of immuno-competent cells belonging to both innate and adaptive immunity, therefore triggering inflammatory and immune responses to the microbial invaders.Another subset of non-microbial “danger signals” has been more recently recognized. The term “alarmins” has been proposed at the last EMBO Workshop on Innate Danger Signals and HMGB1 for these molecules [19]. Indeed, cell and tissue damages are not only caused by pathogens but also by physical stress (wounding, cold or heat etc...), radiations, chemicals, nutrients or oxygen starvation. These traumas trigger a non-septic immune/inflammatory response and the alarmins would be the endo-genous molecules that initiate this process. Exogenous PAMPS and endo-genous “alarmins” are therefore consi-dered as two subgroups of a larger set of molecules, the Damage Associated Molecular Patterns (DAMPs) [19].
Alarmins share several characteristics [ 19,20]:
a They are from cellular origin.
b They are rapidly released by cell dying through non-programmed cell processes, but they are usually not released during apoptosis.
c They should be secreted by living immuno-competent cells following activation.
d They activate cells from the innate immunity so they can initiate the adaptive response.
e Finally, they promote the healing and reconstruction of the damages tissues.
Among other putative candidates, HMGB1 fully meets these criteria and it is now considered as the leading member of this new group of molecules.