Extracellular Heat Shock Proteins as Stress Communication Signals

Extracellular Heat Shock Proteins as a Natural Protector of Cells and Organisms: A Review of Recent Studies

“…In some settings proinflammatory effects were seen, but such effects typically are weak when the doses of HSPs are physiological. This is not surprising because, while true DAMPs, such as high mobility group 1 (HMGB1), are normally located intracellularly, HSPs, such as Hsp60 and Hsp70, are present in the extracellular space as well [7].…”

“…Particularly under certain pathological conditions or in response to cellular stress, a number of HSP members can be found in extracellular space, as a free soluble protein, or as a part of extracellular matrix (ECM) [7]. It is likely that HSPs, which lack an N-terminal hydrophobic signal sequence, employ several non-canonical secretory pathways, including secretory lysosomes [77].…”

“…Upon cell stress, relocation to the cell surface and eventually release into the extracellular space occur for many HSPs [7]. Recent important developments of this field involve the studies by Srivastava and coworkers that showed that HSP-peptide complexes prepared from tumors can enter antigen presenting cells (APCs) for re-presentation on both MHC class I and class II, and induce antitumor immunity [8,9].…”

“…It is of importance to consider the typical cellular localization and functions of HSPs. The HSPs called glucose regulated protein (Grp), such as Grp78 (a member of Hsp70 family), Grp94/gp96 (Hsp90 family) and Grp170 (Hsp100 family) resided in ER and participate in quality control of protein folding in ER [7]. Broadly, Hsp70 an Hsp90 normally participate in antigen processing and presentation and in T cell polarization (the 'relay line model' proposed by Srivastava and coworkers) [13][14][15].…”