Time course and contact dependence of allogeneic lymphocyte-induced human aortic endothelial cell-derived interleukin-6.
Vascular endothelial cells secrete the pluripotent cytokine interleukin-6, and the induction of this secretion can be regulated by a number of other immune-related cytokines. To determine whether a cellular alloimmunologic response to vascular endothelial cells alters the expression of interleukin-6 production by endothelial cells, we cocultured peripheral blood lymphocytes with a pool of human aortic endothelial cells. In response to the pool of allogeneic human aortic endothelial cells, lymphocytes from 10 separate donors proliferated to varying degrees after 5 days of coculturing. After 20 hours, human aortic endothelial cell-derived messenger RNA coding for interleukin-6 increased an average of 96% after exposure to allogeneic lymphocytes and the amount of biologically active interleukin-6 released into the media increased 69%. The kinetics of human aortic endothelial cell interleukin-6 messenger RNA expression in response to lymphocytes from an additional three donors was determined over a 48-hour period. Human aortic endothelial cell interleukin-6 messenger RNA increased approximately threefold over control, as early as 2 hours after exposure to allogeneic lymphocytes and returned toward control levels by 48 hours. Activation of six additional isolates of lymphocytes with phorbol myristate acetate before exposure to human aortic endothelial cells resulted in an increase in human aortic endothelial cell-derived interleukin-6 bioactivity regardless of whether the cells were in direct contact with the human aortic endothelial cells, but the interleukin-6 level increase was approximately twofold higher in those cocultures where there was direct contact. These data show that allogeneic lymphocytes have the potential of regulating vascular endothelial cell-derived interleukin-6, and direct lymphocyte-endothelial cell contact appears to be required for optimal interleukin-6 induction in this in vitro system.
Morris
T E
TE
Immunobiology Research Laboratory, Oregon Cardiac Transplant Program, Portland.
Shipley
G D
GD
Wagner
C R
CR
Hefeneider
S H
SH
Hosenpud
J D
JD
D001011:Aorta / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger