The modulation of tissue factor by endothelial cells during heat shock.
Tissue factor (TF) initiates the extrinsic coagulation cascade on the surface of macrophages and endothelial cells. In septic patients, the extrinsic coagulation cascade is activated. When septic patients are febrile, mortality is decreased. The purpose of this study was to investigate the role of elevated temperatures on TF expression by endothelial cells during a sepsis-like challenge. Human endothelial vein cells (HUVECs) were incubated with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) for 0, 2, 4, 6, or 8 h. At the 0-h time point, some HUVECs were heat shocked at 43 degrees C for 2 h and then recovered at 37 degrees C for 0, 2, 4, or 6 h. Heat-shocked and non-heat-shocked LPS-stimulated HUVECs were analyzed for TF-specific mRNA expression by ribonuclease protection assay (RPA), surface TF expression by flow cytometry, and TF activity by a two-stage clotting assay. Heat shocked LPS-stimulated HUVECs expressed significantly reduced TF-specific mRNA, TF surface protein levels, and TF surface activity when compared with non-heat-shocked, LPS-stimulated HUVECs (p < 0.0125, p < 0.0125, and p < 0.0001, respectively; repeated measures analysis of variance, ANOVA). If heat shock models elevated core temperature, these results suggest that fever may protect the host during sepsis by reducing TF activity on the surface of endothelial cells.
Basi
David L
DL
University of Minnesota School of Dentistry, Department of Oral Sciences, Minneapolis, Minnesota 55455, USA.
Ross
Karen F
KF
Hodges
James S
JS
Herzberg
Mark C
MC
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics; D018869:Heat-Shock Response; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000502:physiology*
D017931:DNA Primers; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D013925:Thromboplastin