Osornio-Vargas A R, Lindroos P M, Coin P G, Badgett A, Hernandez-Rodriguez N A, Bonner J C
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Am J Physiol. 1996 Jul;271(1 Pt 1):L93-9. doi: 10.1152/ajplung.1996.271.1.L93.
Alteration of the platelet-derived growth factor (PDGF) receptor system could be important in enhancing the mitogenic and chemotactic potential of lung fibroblasts during pulmonary fibrogenesis. We previously reported that interleukin-1 beta (IL-1 beta) upregulates the PDGF receptor-alpha (PDGFR-alpha) gene, and in this study we sought to establish the importance of the PDGFR-alpha relative to the PDGFR-beta in mediating a chemotactic response to PDGF-AA, -AB, and -BB. Pretreatment of fibroblasts for 24 h with IL-1 beta increased chemotaxis to all three PDGF isoforms. IL-1 beta pretreatment markedly increased the maximal number of 125I-labeled PDGF-AA binding sites but did not change the number of 125I-PDGF-AB or PDGF-BB sites. However, IL-1 beta increased 125I-PDGFR-AB affinity twofold. Neomycin (5 mM) was used as a PDGFR-alpha antagonist and completely blocked 125I-PDGF-AA binding and PDGF-AA-induced chemotaxis. The binding affinity of 125I-PDGF-AB and 125I-PDGF-BB was increased two-to threefold by neomycin, and chemotaxis to PDGF-AB and PDGF-BB was enhanced. These results define a role for the PDGFR-alpha as a regulatory receptor subtype that is necessary for PDGF isoforms to exert maximal chemotaxis.
血小板衍生生长因子（PDGF）受体系统的改变在肺纤维化形成过程中增强肺成纤维细胞的促有丝分裂和趋化潜力方面可能具有重要意义。我们先前报道白细胞介素-1β（IL-1β）上调PDGF受体-α（PDGFR-α）基因，在本研究中，我们试图确定相对于PDGFR-β，PDGFR-α在介导对PDGF-AA、-AB和-BB的趋化反应中的重要性。用IL-1β预处理成纤维细胞24小时可增加对所有三种PDGF亚型的趋化性。IL-1β预处理显著增加了125I标记的PDGF-AA结合位点的最大数量，但未改变125I-PDGF-AB或PDGF-BB位点的数量。然而，IL-1β使125I-PDGFR-AB亲和力增加了两倍。新霉素（5 mM）用作PDGFR-α拮抗剂，完全阻断了125I-PDGF-AA结合和PDGF-AA诱导的趋化性。新霉素使125I-PDGF-AB和125I-PDGF-BB的结合亲和力增加了两到三倍，并增强了对PDGF-AB和PDGF-BB的趋化性。这些结果确定了PDGFR-α作为一种调节性受体亚型的作用，它是PDGF亚型发挥最大趋化性所必需的。
