Kumar R K, Maronese S E, Hassim Z
Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia.
Cell Biol Toxicol. 1998 Aug;14(4):293-9. doi: 10.1023/a:1007439109686.
Mitogens of the EGF family may play an important role in regulating the proliferation of airway epithelial cells (AEC). We examined the production of autocrine mitogenic activity by mouse AEC cultured from explants of tracheal tissue. DNA synthesis by growth-arrested AEC was stimulated by conditioned media from cells maintained in serum-free culture without exogenous growth factors. The mitogenic activity was blocked by a specific inhibitor of the EGF receptor tyrosine kinase. Furthermore, conditioned media from AEC contained molecular species that could compete with radiolabeled EGF in a receptor binding assay. However, mitogenic activity was not blocked by neutralizing antibodies to EGF or to transforming growth factor-alpha, but was partly inhibited by co-incubation with heparin, suggesting that it might be due to a heparin-binding member of the EGF family. The activity was potentiated by co-incubation with IGF-1, analogous to the potentiation by IGF-1 of the mitogenic activity of EGF for AEC. Moreover, the autocrine mitogen produced by AEC exhibited cooperative interaction with the mitogenic activity in conditioned media from growth factor-deprived mouse lung fibroblasts, consistent with the hypothesis that interactions with mesenchymal cells could influence the proliferation of AEC in vivo.
表皮生长因子（EGF）家族的促分裂原可能在调节气道上皮细胞（AEC）增殖中发挥重要作用。我们检测了从小鼠气管组织外植体培养的AEC产生自分泌促有丝分裂活性的情况。在无外源性生长因子的无血清培养条件下，生长停滞的AEC的DNA合成受到来自细胞的条件培养基的刺激。促有丝分裂活性被EGF受体酪氨酸激酶的特异性抑制剂阻断。此外，AEC的条件培养基含有能在受体结合试验中与放射性标记的EGF竞争的分子种类。然而，促有丝分裂活性未被针对EGF或转化生长因子-α的中和抗体阻断，但与肝素共同孵育可部分抑制该活性，提示其可能归因于EGF家族的一种肝素结合成员。与胰岛素样生长因子-1（IGF-1）共同孵育可增强该活性，类似于IGF-1对EGF促AEC有丝分裂活性的增强作用。此外，AEC产生的自分泌促分裂原与生长因子缺乏的小鼠肺成纤维细胞的条件培养基中的促有丝分裂活性表现出协同相互作用，这与与间充质细胞的相互作用可能在体内影响AEC增殖的假说一致。
