Platelet-derived growth factor stimulates mouse 3T3 cell mitogenesis and leukocyte chemotaxis through different structural determinants.

Platelet-derived growth factor stimulates mouse 3T3 cell mitogenesis and leukocyte chemotaxis through different structural determinants.
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血小板衍生生长因子通过不同的结构决定因素刺激小鼠 3T3 细胞有丝分裂和白细胞趋化性。

DOI:
10.1172/jci111135
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发表时间:
1983
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Goetzl,EJ
Goetzl,EJ
中科院分区:
--
文献类型:
--
作者:
Williams,LT;Antoniades,HN;Goetzl,EJ

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血小板衍生生长因子(PDGF)既能刺激成纤维细胞增殖,又能促进白细胞趋化。在这项研究中,我们比较了天然PDGF和还原PDGF的促有丝分裂和趋化活性。将PDGF(MR=32,000)还原为其组成的多肽(MR=14,000和17,000)导致失去刺激Balb/c 3T3细胞增殖的能力。然而,还原的PDGF几乎保留了其作为人中性粒细胞和单核细胞趋化剂的所有活性。中性粒细胞和单核细胞在0.08 nM和0.1 nM的浓度下,对天然和还原的PDGF均有半最大趋化反应。对还原PDGF的最大趋化反应至少与对天然PDGF的最大趋化反应相同。天然和还原的PDGF均能刺激中性粒细胞释放溶酶体酶--β-氨基葡萄糖苷酶,在0.1 nM以下有半最大反应。然而,PDGF(和还原的PDGF)对该酶的净最大释放量明显低于最大浓度的趋化肽N-甲酰甲硫基-亮氨酰苯丙氨酸的刺激。这些结果表明,3T3细胞对PDGF的增殖反应和白细胞对PDGF的趋化反应需要不同的结构决定因素。
Platelet-derived growth factor (PDGF) stimulates both proliferation of fibroblasts and chemotaxis of leukocytes. In this study we compared the mitogenic and chemotactic activities of native PDGF and reduced PDGF. Reduction of PDGF (Mr = 32,000) to its constituent polypeptides (Mr = 14,000 and 17,000) caused a loss of the ability to stimulate proliferation of Balb/c 3T3 cells. However, reduced PDGF retained virtually all of its activity as a chemotactic agent for human neutrophils and monocytes. A half-maximal chemotactic response to both native and reduced PDGF occurred at a concentration of approximately 0.08 nM for neutrophils and 0.1 nM for monocytes. The maximal chemotactic response to reduced PDGF was at least as great as the maximal response to native PDGF. Both native and reduced PDGF stimulated the release of the lysosomal enzyme, beta-glucosaminidase, from neutrophils with a half-maximal response at less than 0.1 nM. However, the net maximum release of this enzyme by PDGF (and reduced PDGF) was significantly less than that stimulated by a maximal concentration of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine. These results indicate that different structural determinants are required for the proliferative response of 3T3 cells to PDGF and for the chemotactic response of leukocytes to PDGF.