Xy. Wang et al., Effect of fever-like whole-body hyperthermia on lymphocyte spectrin distribution, protein kinase C activity, and uropod formation, J IMMUNOL, 162(6), 1999, pp. 3378-3387
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.