Hypothermia inhibits human E-selectin transcription.
During endothelial cell activation, the formation and expression of E-selectin require transcriptional activation of the E-selectin gene, mediated by the coordinated action of several transcription factors and cis-acting elements in its 5'-flanking region. It is reported that in vitro hypothermia (25 degrees C) transiently inhibits transcriptional activation and surface expression of E-selectin as well as neutrophil adherence to cultured human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS), interleukin-1 (IL-1), or tumor necrosis factor (TNF). Rewarming HUVECs treated with LPS, IL-1, or TNF to 37 degrees C restores E-selectin transcript accumulation, E-selectin surface expression, and neutrophil adherence to HUVECs at levels equivalent to similarly treated HUVECs maintained at 37 degrees C continuously. Despite the absence of detectable E-selectin transcription at 25 degrees C, activation of the transcription factor NF-kappaB still occurred in HUVECs treated with LPS, IL-1, or TNF, indicating that signal transduction was not blocked by hypothermia. It is concluded that neutrophil adherence to activated endothelium mediated by E-selectin is reversibly inhibited by hypothermia. The protective effect of hypothermia clinically (e.g., cardiopulmonary bypass) may, in part, be mediated by transiently inhibiting the expression of an endothelial cell activation phenotype.
Haddix
T L
TL
Department of Pathology, University of Washington, Seattle, 98195, USA.
Pohlman
T H
TH
Noel
R F
RF
Sato
T T
TT
Boyle
E M
EM
Verrier
E D
ED
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D003080:Cold Temperature; D019040:E-Selectin / Q000235:genetics* / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D018922:HL-60 Cells / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007035:Hypothermia / Q000503:physiopathology*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha