Winzen R, Wallach D, Engelmann H, Nophar Y, Brakebusch C, Kemper O, Resch K, Holtmann H
Institute of Molecular Pharmacology, Medical School, Hannover, FRG.
J Immunol. 1992 Jun 1;148(11):3454-60.
Expression of the two known receptors for TNF was studied in the promyelocytic leukemia cell line HL-60 before and after differentiation of the cells along the granulocyte lineage (induced by incubation with retinoic acid), or along the macrophage lineage (induced by incubation with the phorbol diester, PMA). The extent of inhibition of TNF binding by receptor-specific antisera, as well as the size of the complexes formed after cross-linking TNF to its receptors on intact cells, indicated that both receptor species were expressed on the surface of the undifferentiated HL60 cells. Differentiation into granulocyte-like cells resulted in some increase in TNF binding. The increase was apparently due to enhanced expression of the 75-kDa TNF-R, whereas the amounts of the 55-kDa TNF-R did not change significantly. In contrast, in HL-60 cells induced to differentiate into macrophage-like cells, expression of the 55-kDa TNF-R species was completely abolished. The pattern of TNF-R expression in the differentiated HL-60 cells was similar to that observed in leukocytes isolated from peripheral blood: on granulocytes, there were about equal amounts of both receptor species, whereas on monocytes the 75-kDa receptor was predominant. The loss of 55-kDa receptors during differentiation of HL-60 cells into macrophage-like cells was accompanied by a pronounced decrease in the level of the mRNA for that receptor, suggesting that at least part of the change in TNF-R expression is due to mechanisms that control the amounts of receptor mRNA. Although little is yet known regarding the functional differences between the two receptor species, marked changes in the pattern of their expression, as observed during HL-60 cell differentiation, are likely to alter the kind of response of the cells to TNF and may therefore play an important role in the coordination of TNF effects in the organism.
在早幼粒细胞白血病细胞系HL - 60中，研究了肿瘤坏死因子（TNF）两种已知受体在细胞沿粒细胞谱系（用视黄酸孵育诱导）或巨噬细胞谱系（用佛波酯PMA孵育诱导）分化前后的表达情况。受体特异性抗血清对TNF结合的抑制程度，以及完整细胞上TNF与其受体交联后形成的复合物大小，表明两种受体均表达于未分化的HL60细胞表面。分化为粒细胞样细胞导致TNF结合略有增加。这种增加显然是由于75 kDa TNF受体的表达增强，而55 kDa TNF受体的量没有显著变化。相反，在诱导分化为巨噬细胞样细胞的HL - 60细胞中，55 kDa TNF受体的表达完全消失。分化后的HL - 60细胞中TNF受体的表达模式与从外周血分离的白细胞中观察到的相似：在粒细胞上，两种受体的量大致相等，而在单核细胞上，75 kDa受体占主导。HL - 60细胞分化为巨噬细胞样细胞过程中55 kDa受体的丢失伴随着该受体mRNA水平的显著下降，这表明TNF受体表达的至少部分变化是由于控制受体mRNA量的机制所致。尽管对于两种受体之间的功能差异知之甚少，但如在HL - 60细胞分化过程中观察到的，它们表达模式的显著变化可能会改变细胞对TNF的反应类型，因此可能在机体中TNF效应的协调中起重要作用。
