The role of extracellular heat shock proteins in cellular inflammation and injury

Ferruccio Ritossa first observed a novel hyperthermia-dependent puffing pattern in the giant chromosomes from the salivary glands of Drosophila melanogaster in 1962 [1]. By a chance occurrence, a colleague accidentally increased the temperature of one of the incubators in which he kept his specimens, and the following morning Ritossa discovered a new puffing pattern that had not been there on the previous day. Realizing the mistake, Ritossa conducted additional, properly controlled experiments and subsequently linked this new chromosomal puffing pattern with the expression of a specific group of proteins that he fittingly called heat shock proteins (HSP) [1,2]. Since Ritossa's seminal observations in 1962, subsequent investigations into this area have continued, resulting in a growing interest in what is now commonly referred to as the heat shock response. The heat shock response is characterized by the rapid expression of a unique set of proteins collectively known as HSP [3, 4]. The structure, mode of regulation, and function of HSP are highly conserved among different species, and HSP have been identified in virtually all eukaryotic and prokaryotic species examined to date. While classically described as a response to thermal stress (hence the term heat shock response), HSP can be induced by a wide variety of non-thermal stressors and pharmacological agents (Table 1). These proteins range in molecular weight from 7 to 110 kDa and are found in virtually every cellular compartment, including the nucleus, cytoplasm, and mitochondria (Table 2). By convention, the stress proteins are classified according to their molecular weight, e.g. HSP25, HSP32, HSP47, HSP60, HSP70, HSP90, and HSP110.