Khew-Goodall Y, Butcher C M, Litwin M S, Newlands S, Korpelainen E I, Noack L M, Berndt M C, Lopez A F, Gamble J R, Vadas M A
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia.
Blood. 1996 Feb 15;87(4):1432-8.
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.
内皮细胞表面表达的P-选择素在体外介导白细胞黏附，在体内介导白细胞滚动。此前已鉴定出几种可诱导内皮细胞（EC）表面P-选择素表达的诱导剂，所有这些诱导剂均会使P-选择素在细胞表面短暂表达，持续时间从几分钟到几小时不等。我们现在表明，一种T淋巴细胞产物白细胞介素-3（IL-3）可刺激长期培养的内皮细胞（人脐静脉内皮细胞，HUVEC）。IL-3诱导细胞表面P-选择素表达分两个阶段。最初在10分钟时出现一个峰值，随后在添加IL-3后16小时开始出现持续上调，并至少持续4天。添加48小时IL-3诱导的P-选择素表达水平与用凝血酶处理HUVEC 10分钟诱导的水平相似，并且先添加48小时IL-3再添加10分钟凝血酶的效果是相加的。用抗IL-3受体α链的阻断单克隆抗体预处理内皮细胞可阻断IL-3诱导的细胞表面P-选择素表达。脂多糖（LPS）、肿瘤坏死因子α（TNFα）以及活性降低的IL-3突变体与HUVEC孵育48小时后均未诱导细胞表面P-选择素表达，这表明该效应是IL-3特有的。与IL-3孵育16小时后细胞表面P-选择素表达的增加伴随着稳态mRNA水平的类似长时间增加，而在添加IL-3后10分钟未观察到这种情况。由于T淋巴细胞浸润是慢性炎症的一个标志，我们的观察结果表明，T淋巴细胞分泌的IL-3可能在慢性炎症期间维持炎症状态。
