T-LYMPHOCYTES SYNTHESIZE AND EXPORT HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR, MITOGENS FOR VASCULAR CELLS AND FIBROBLASTS - DIFFERENTIAL PRODUCTION AND RELEASE BY CD4+ AND CD8+ T-CELLS
T-LYMPHOCYTES SYNTHESIZE AND EXPORT HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR, MITOGENS FOR VASCULAR CELLS AND FIBROBLASTS - DIFFERENTIAL PRODUCTION AND RELEASE BY CD4+ AND CD8+ T-CELLS
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DOI：
10.1073/pnas.91.8.2890
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发表时间：
1994-04-12
影响因子：
11.1
通讯作者：
KLAGSBRUN, M
中科院分区：
文献类型：
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作者：
BLOTNICK, S;PEOPLES, GE;KLAGSBRUN, M
T淋巴细胞浸润伤口、肿瘤和动脉粥样硬化斑块，这是以血管细胞和成纤维细胞迁移和增殖为特征的病理生理过程。尽管已知T淋巴细胞能够产生炎症细胞的细胞因子，但尚未证明它们合成对血管细胞和成纤维细胞有丝分裂作用的生长因子。我们证明从正常人外周血中分离的培养 T 淋巴细胞合成并输出两种特征良好的生长因子，即肝素结合表皮生长因子样生长因子 (HB-EGF) 和碱性成纤维细胞生长因子 (bFGF)。该结论基于 mRNA 表达分析、肝素亲和层析谱、靶细胞特异性以及特异性中和抗体的功能抑制。不典型的是，大量 T 细胞衍生的 bFGF 样活性似乎持续释放到条件培养基中，几乎与 T 细胞裂解物中的释放量一样多。 bFGF 由纯化的 CD4+ 和 CD8+ T 细胞合成和输出，而 HB-EGF 主要由 CD4+ T 细胞合成和输出。 T 细胞衍生的 HB-EGF 和 bFGF 活性是成纤维细胞和平滑肌细胞的有效有丝分裂原，bFGF 样活性对内皮细胞也具有促有丝分裂作用。这些结果表明，T 淋巴细胞可能通过局部作用将血管细胞生长因子递送至组织，在介导与动脉粥样硬化相关的平滑肌增生以及与伤口愈合和肿瘤生长相关的血管生成中发挥关键作用。
T lymphocytes infiltrate wounds, tumors, and atherosclerotic plaques, pathophysiological processes characterized by the migration and proliferation of vascular cells and fibroblasts. Although T lymphocytes are known to produce cytokines for inflammatory cells, it has not been demonstrated that they synthesize growth factors that are mitogenic for vascular cells and fibroblasts. We demonstrate that cultured T lymphocytes isolated from normal human peripheral blood synthesize and export two well-characterized growth factors, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and basic fibroblast growth factor (bFGF). This conclusion is based on mRNA expression analysis, heparin-affinity chromatography profiles, target-cell specificity, and functional inhibition by specific neutralizing antibodies. Atypically, a substantial amount of T-cell-derived bFGF-like activity appears to be constitutively released into conditioned medium, almost as much as is associated with T-cell lysates. bFGF is synthesized and exported by purified CD4+ and CD8+ T cells, whereas HB-EGF is synthesized and exported primarily by CD4+ T cells. The T-cell-derived HB-EGF and bFGF activities are potent mitogens for fibroblasts and smooth muscle cells, and the bFGF-like activity is also mitogenic for endothelial cells. These results suggest that T lymphocytes may play key roles in mediating smooth muscle hyperplasia associated with atherosclerosis and in angiogenesis associated with wound healing and tumor growth by acting locally to deliver vascular-cell growth factors to tissues.