FEVER-RANGE HYPERTHERMIA ENHANCES L-SELECTIN-DEPENDENT ADHESION OF LYMPHOCYTES TO VASCULAR ENDOTHELIUM

The L-selectin leukocyte adhesion molecule prays an important role in controlling leukocyte extravasation in peripheral lymph nodes and at s ites of tissue injury or infection. Although febrile responses during infection and inflammation are associated with enhanced immune activit y, the contribution of fever-range temperatures to controlling lymphoc yte recruitment to tissues has not been previously examined. In this r eport we provide evidence that direct exposure of lymphocytes to fever -range temperatures (38-41 degrees C) in vitro for 9 to 24 h resulted in a >100% increase in L-selectin-dependent adhesion of these cells to lymph node high endothelial venules (HEV). Moreover, culture of lymph ocytes under hyperthermia conditions markedly enhanced the ability of these cells to traffic in an L-selectin-dependent manner to peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. In contrast , febrile temperatures did not increase LFA-I function as assessed by measuring lymphocyte adhesion to ICAM-1-3T3 transfectants. Fever-range hyperthermia further did not increase L-selectin surface density on l ymphocytes or L-selectin-dependent recognition of soluble carbohydrate substrates; however, a marked increase in ultrastructural immuno-gold -labeling of L-selectin was observed in response to thermal stimuli. T hese results suggest that elevated temperatures enhance L-selectin adh esion and/or avidity through the regulation of L-selectin conformation or organization in the plasma membrane. Finally, the observed thermal effects on L-selectin adhesion were attributed to soluble factors in the conditioned medium of heat-treated cells. Taken together, these da ta provide new insight into the potential physiologic role of the febr ile response in enhancing lymphocyte recruitment to tissues through th e regulation of L-selectin adhesion.