Extracellular Heat Shock Proteins as Stress Communication Signals

Abstract

Intercellular communication is a fundamental process necessary to maintain homeostasis and to mount an orchestrated response to stress. Although heat shock proteins (HSP) play a critical role by participating in the repair of damaged products as a result of the stress in the intracellular milieu, it is now evident that they play an alternative role when they escape from the cells and are placed in circulation, participating in a systemic stress response. Extracellular HSP appear as signaling molecules involved in intercellular communication during stress conditions. They have been found to modulate the function of many target cells. Moreover, extracellular HSP have been detected in several biological fluids, particularly from patients suffering from a large number of maladies. Extracellular HSP are released by many cell types and by several mechanisms, including passive dissemination after necrosis and active export by a nonclassical secretory pathway. Among several potential mechanisms for the export of HSP, their release associated with extracellular vesicles has gained increasing support. The appearance of extracellular vesicles containing HSP emerges as a new form of cellular communication during stress conditions directed at avoiding the propagation of the insult.