REGULATION OF ARACHIDONIC ACID METABOLISM IN MONOCYTES BY TYROSINE PHOSPHORYLATIO

用c-fms转染小鼠造血细胞系32 D， 编码CSF-1受体，一种酪氨酸激酶（TK）。在没有 CSF-1转染的细胞显示中等水平的花生四烯酸（A.A.） 释放并产生大量的前列腺素E2（PGE 2）， 与原始细胞系比较。转染细胞暴露于 CSF-1在诱导花生四烯酸释放显著增加的同时， 然而，导致PGE 2产生的抑制。添加ST 638， 一种酪氨酸激酶抑制剂，在没有 CSF-1在10 - 60分钟内抑制PGE_2的产生。其添加 在CSF-1存在的情况下对相同的细胞诱导相反的效果，但是 需要更长的治疗时间（24小时）。在任一细胞类型中，A.A.释放 不受这种物质的影响。这些数据表明，CSF-1受体可能 调节环氧合酶活性。CSF-1受体在不同细胞因子中的作用 在存在或不存在CSF-I的情况下PGE的产生以及相反的作用 酪氨酸激酶抑制剂对前列腺素E2的抑制作用表明， 或者受体-配体复合物是一种活性的，但不同的信号， 通过酪氨酸磷酸化。

The mouse hematopoietic cell line, 32D, was transfected with c-fms, which encode for the CSF-1 receptor, a tyrosine kinase (TK) . In the absence of CSF-1, transfected cells show moderate levels of arachidonic acid (A.A.) release and produce a substantial amount of prostaglandin E2 (PGE2) in comparison with the original cell line. Exposure of transfected cells to CSF-1, while inducing a substantial increase in arachidonate release, nevertheless resulted in inhibition of PGE2 production. Addition of ST638, a tyrosine kinase inhibitor, to cells transfected with c-fms in the absence of CSF-1 inhibited PGE2, production within 10 to 60 minutes. Its addition to the same cells in the presence of CSF-1 induced an opposite effect, but required longer treatment (24 hours). In either cell type, A.A. release was not affected by this agent. These data indicate that CSF-1 receptor may regulate cyclooxygenase activity. The different effect of CSF-1 receptor on PGE, production in the presence or absence of CSF-I and the opposite effect of a tyrosine kinase inhibitor on PGE2 suggest that both the receptor alone or the receptor-ligand complex transduce an active, but different, signal through tyrosine phosphorylation.