Lebeurier I, Raclet L, Amiral J, Caen J P, Han Z C
Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France.
J Lab Clin Med. 1996 Feb;127(2):179-85. doi: 10.1016/s0022-2143(96)90076-1.
We have previously shown that platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) inhibit the growth of the human erythroleukemia cell line (HEL). We further studied the effect of PF4, beta-TG, and various related peptides on human leukemic lineages to determine the specificity and the relationship between the inhibitory activity and the molecular structure of PF4. The results showed that PF4 and beta-TG had an inhibitory activity on the megakaryocytic growth. Furthermore, peptides corresponding to the 1-24 and 13-24 residues but not to the 16-24 residue of the PF4 C-terminal region, the 21-29 and 20-28 C-terminal region of beta-TG and IL-8, inhibited only the megakaryocytic cell growth. Interestingly, when Gln and Asn located at positions 15 and 24, respectively, of the PF4 C-terminal region were replaced by Glu and Asp (C13-24DE), an increase in the inhibitory activity was observed. Moreover, the 13-24 monomeric form (13-24M) and modified form (13-24A), where a cysteine in C-terminal position 19 was substituted by arginine, were no longer active. These results suggest that the inhibitory activity of PF4 and its related peptides might be localized in their 13-24 C-terminal region and that a dimeric structure seems to be necessary to exert inhibitory activity.
我们之前已经表明，血小板因子4（PF4）和β-血小板球蛋白（β-TG）可抑制人红白血病细胞系（HEL）的生长。我们进一步研究了PF4、β-TG及各种相关肽对人白血病谱系的影响，以确定PF4抑制活性的特异性及其与分子结构之间的关系。结果显示，PF4和β-TG对巨核细胞生长具有抑制活性。此外，与PF4 C末端区域的1-24和13-24残基相对应但与16-24残基不对应的肽、β-TG和IL-8的21-29和20-28 C末端区域的肽，仅抑制巨核细胞的生长。有趣的是，当PF4 C末端区域第15位和第24位的谷氨酰胺和天冬酰胺分别被谷氨酸和天冬氨酸取代（C13-24DE）时，观察到抑制活性增强。此外，13-24单体形式（13-24M）和修饰形式（13-24A）（其中C末端第19位的半胱氨酸被精氨酸取代）不再具有活性。这些结果表明，PF4及其相关肽的抑制活性可能定位于其13-24 C末端区域，并且二聚体结构似乎是发挥抑制活性所必需的。
