Chronic expression of P-selectin on endothelial cells stimulated by the T-cell cytokine, interleukin-3.
P-selectin expressed on the surface of endothelium mediates leukocyte adhesion in vitro and rolling in vivo. Several inducers of cell-surface P-selectin expression on endothelial cells (EC) have previously been identified, all of which yield transient cell-surface expression of P-selectin lasting minutes to a few hours. We now show that a T-lymphocyte product, interleukin-3 (IL-3), stimulates the long-term endothelial cells (HUVEC). IL-3 induced cell-surface P-selectin expression in two phases. An initial peak at 10 minutes was followed by a prolonged upregulation beginning 16 hours after IL-3 addition and lasting at least 4 days. The level of P-selectin expression induced by IL-3 added for 48 hours was similar to that induced by treatment of HUVEC for 10 minutes with thrombin, and the effect of adding IL-3 for 48 hours followed by thrombin for 10 minutes was additive. Induction of cell-surface P-selectin expression by IL-3 was blocked by pretreatment of EC with a blocking monoclonal antibody against the IL-3 receptor alpha-chain. Lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) and a mutant form of IL-3 with decreased potency did not induce cell-surface P-selectin expression after 48 hours' incubation with HUVEC, suggesting that the effect was specific to IL-3. The increase in cell-surface P-selectin expression occurring after 16 hours of incubation with IL-3 was accompanied by a similar prolonged increase in the steady-state mRNA level that was not observed at 10 minutes after IL-3 addition. As T-lymphocyte infiltration is a hallmark of chronic inflammation, our observations suggest that the secretion of IL-3 by T lymphocytes may serve to maintain the inflammatory state during chronic inflammation.
Khew-Goodall
Y
Y
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia.
Butcher
C M
CM
Litwin
M S
MS
Newlands
S
S
Korpelainen
E I
EI
Noack
L M
LM
Berndt
M C
MC
Lopez
A F
AF
Gamble
J R
JR
Vadas
M A
MA
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
D007377:Interleukin-3; D019007:P-Selectin; D012333:RNA, Messenger; D013917:Thrombin