Effect of fever-like whole-body hyperthermia on lymphocyte spectrin distribution, protein kinase C activity, and uropod formation

Regional inflammation and systemic fever are hallmarks of host immune respo nses to pathogenic stimuli. Although the thermal element of fever is though t to enhance the activity of immune effector tells, it is unclear what the precise role of increased body temperatures is on the activation state and effector functions of lymphocytes. We report here that mild, fever-like who le body hyperthermia (WBH) treatment of mice results in a distinct increase in the numbers of tissue lymphocytes with polarized spectrin cytoskeletons and uropods, as visualized in situ, WBH also induces a coincident reorgani zation of protein kinase C (PKC) isozymes and increased PKC activity within T cells, These hyperthermia-induced cellular alterations are nearly identi cal with the previously described effects of Ag- and mitogen-induced activa tion on lymphocyte spectrin and PKC, Immunoprecipitation studies combined w ith dual staining and protein overlay assays confirmed the association of P KC beta and PKC theta with spectrin following its reorganization. The recep tor for activated C kinase-l was also found to associate with the spectrin- based cytoskeleton, Furthermore, all these molecules (spectrin, PKC beta, P KC theta, and receptor for activated C kinase-1) cotranslocate to the uropo d, Enhanced intracellular spectrin phosphorylation upon WBII treatment of l ymphocytes was also found and could be blocked by the PKC inhibitor bisindo lylmaleimide I (GF109203X), These data suggest that the thermal element of fever, as mimicked by these studies, can modulate critical steps in the sig nal transduction pathways necessary for effective lymphocyte activation and function. Further work is needed to determine the cellular target(s) that transduces the signaling pathway(s) induced by hyperthermia.