Stabilization by heparin of acidic fibroblast growth factor mitogenicity for human endothelial cells in vitro.
Stabilization by heparin of acidic fibroblast growth factor mitogenicity for human endothelial cells in vitro.
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肝素对人内皮细胞体外酸性成纤维细胞生长因子有丝分裂原性的稳定作用。
DOI：
10.1002/jcp.1041400306
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发表时间：
1989
影响因子：
5.6
通讯作者：
Levine,EM
中科院分区：
文献类型：
--
作者：
Mueller,SN;Thomas,KA;DiSalvo,J;Levine,EM
研究了肝素和其他糖胺聚糖(GAG)对酸性成纤维细胞生长因子(AFGF)有丝分裂活性和稳定性的影响。以分离的成人髂动静脉内皮细胞(AHECs)为靶细胞，检测aFGF的促有丝分裂活性。在大多数实验中，使用了从牛脑中纯化的aFGF；在一些实验中，使用了重组的牛aFGF，得到了定性上相似的结果。在肝素存在下，牛aFGF0.5~1.0 ng/ml(30~60 pm)诱导AHEC在4天内的最大生长量的一半取决于所测试的细胞系；在无肝素的情况下，当aFGF值低于10~20 ng/ml时，不能观察到显著的生长。肝素的这种作用在0.10~10μg/ml(一半最大剂量，2μg/ml)范围内呈剂量依赖关系。牛aFGF在37℃无细胞培养液中预培养2.5~3h后，对AHECs的促有丝分裂活性下降了50%。相反，在没有细胞的含肝素的培养液中预先孵育的牛aFGF的有丝分裂活性显著稳定(半衰期24-29小时)。在无血清培养液中也观察到了上述作用。几种与肝素结构相关的GAG，如软骨素-4-硫酸盐、软骨素-6-硫酸盐、皮肤素硫酸盐和透明质酸，既不增强也不稳定aFGF的有丝分裂活性。然而，来自牛肺的硫酸肝素被发现在这两种作用中几乎与肝素一样有效。这些数据表明，细胞外和组织相关的肝素硫酸盐对有丝分裂原的结合和稳定可能在AHEC的生长调节中发挥重要作用。
The effects of heparin and other glycosaminoglycans (GAGs) on the mitogenicity and stability of acidic fibroblast growth factor (aFGF) were studied. The mitogenic activity of aFGF was assayed utilizing cultured adult human endothelial cells (AHECs) isolated from iliac arteries and veins as target cells. In most experiments, aFGF purified from bovine brain was employed; in some experiments recombinant bovine aFGF was used and qualitatively similar results were obtained. In the presence of heparin, bovine aFGF at doses between 0.5 and 1.0 ng/ml (30‐60 pM) elicited half the maximum AHEC growth over a 4‐day period depending on the cell line tested; in the absence of heparin, significant growth was not observed at aFGF concentrations less than 10‐20 ng/ml. This effect of heparin was dose‐dependent over the range 0.1‐10 μg/ml (half‐maximum dose, 2 μg/ml). The mitogenic activity of bovine aFGF for AHECs decreased by 50% after preincubation in culture medium without cells at 37°C for 2 ½ to 3 hours. In contrast, the mitogenic activity of bovine aFGF preincubated in the presence of heparin‐containing culture medium without cells was dramatically stabilized (half‐life 24‐29 hours). These effects also were observed in serum‐free medium. Several GAGs structurally related to heparin such as chondroitin‐4‐sulfate, chondroitin‐6‐sulfate, dermatan sulfate, and hyaluronic acid neither potentiated nor stabilized aFGF mitogenic activity. However, heparan sulfate from bovine lung was found to be nearly as active as heparin in both these effects. These data suggest that the binding and stabilization of mitogens by extracellular and tissue‐associated heparan sulfates might play important roles in the regulation of AHEC growth.