DISTRIBUTION OF HSP70, PROTEIN-KINASE-C, AND SPECTRIN IS ALTERED IN LYMPHOCYTES DURING A FEVER-LIKE HYPERTHERMIA EXPOSURE

Many B and T lymphocytes display a significant heterogeneity with resp ect to the subcellular distribution of the cytoskeletal protein spectr in and protein kinase C (PKC), both of which often can be found in a l arge cytoplasmic aggregate in these cell types. In addition to spectri n and PKC, we recently have reported that HSP70 is also a component of this lymphocyte aggregate. Moreover, these three proteins can undergo dynamic and reversible changes in their localization causing ''assemb ly'' of the aggregate in response to various conditions associated wit h lymphocyte activation, indicating that this naturally occurring aggr egate structure is sensitive to activation status. We show here that t he same changes in HSP70/spectrin/PKC localization induced by PKC acti vation also can be caused, in vitro and in vivo, by a mild hyperthermi a exposure, as occurs during a natural fever (39.5-40 degrees C, 2-12 hr). This mild heat exposure also triggers the activation of PKC, a ma jor heat shock response, and lymphocyte proliferation. The increase in PKC activity, HSP70-spectrin-PKC aggregate formation, and heat shock protein expression resulting from exposure to fever-like hyperthermia are all inhibited by calphostin C, a specific inhibitor of PKC. These data demonstrate that changes observed during lymphocyte activation co uld be induced by a mild hyperthermia exposure occurring during a norm al febrile episode. (C) 1997 Wiley-Liss, Inc.