High-mobility group protein B l (HMGB l )a. I s associated with the best -characterized damageassociated molecular pattern (DAMP), detectable in the circulation within 30 minutes of trauma
The best-characterized DAMP in the context of the injuryassociated inflammatory response is high-mobility group protein Bl (HMGBl), which is rapidly released into the circulation within 30 minutes following trauma. Subsequent studies have proven, however, that HMGBl is actively secreted from immune-competent cells stimulated by PAMPs (eg, endotoxin) or by inflammatory cytokines (eg, tumor necrosis factor and interleukin -1). Stressed nonimmune cells, such as endothelial cells, and platelet also actively secrete HMGBI. Finally, passive release of HMGBl can occur following cell death, whether it is programmed or uncontrolled (necrosis). The diverse pro inflammatory biological responses that result from HMGBl signaling include: (1) the release of cytokines and chemokines from macrophage/monocytes and dendritic cells; (2) neutrophil activation and chemotaxis; (3) alterations in epithelial barrier function, including increased permeability; and (4) increased procoagulant activity on platelet surfaces; among others.