Extracellular heat shock protein 70 has novel functional effects on sea urchin eggs and coelomocytes

Numerous reports document that the 70 kDa heat shock proteins are not only intracellular proteins but are also present in blood and other extracellular compartments. How they affect cell function from the extracellular space remains unclear. Using two well-characterized cell types from the sea urchin, we show that extracellular mixtures of the constitutive and inducible forms of the 70 kDa heat shock proteins (Hsc70 and Hsp70, respectively) have dramatic effects on initiation of cell division in fertilized eggs and on the clotting reaction of hypotonically stressed coelomocytes. In suspensions of fertilized eggs to which Hsc70 or a 2:3 mixture of Hsc and Hsp70 was added, progression to the first mitotic division was accelerated. Evidence is provided that the extracellular Hsc70 passes into the egg cells in an unconventional manner, being distributed through the cytoplasm, and that it may alter the intracellular signaling cascade initiated by sperm penetration. In coelomocytes that were stimulated by hypotonic shock to mimic injury, the spreading reaction of the clotting response was significantly inhibited when either Hsp70 or Hsc70 was in the medium. These results suggest that the presence of Hsc and/or Hsp70 in the extracellular fluid may promote mitosis of dividing cells and suppress the reactivity of immune system cells.