FIGURE 2.

Model of S100 protein-mediated metal sequestration and inflammatory response at the site of infection. S100 proteins are released into the extracellular milieu and compete for transition metals with pathogens at the site of infection. Due to their high affinity for transition metals, the transition metals essential to growth and survival are limited at the site of infection, and pathogens are cleared. During infection, S100 proteins stimulate the pro-inflammatory immune response through interaction with RAGE and TLR4. This leads to NF-κB-mediated inflammatory cascade and the production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. This inflammatory response also leads to increased expression of S100 proteins and the start of a positive feedback loop. S100 proteins, such as calprotectin, can also act as reactive oxygen species scavengers and limit collateral damage to the host.