Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-beta 1 therapy.
Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-beta 1 therapy.
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发表时间：
1991-05
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通讯作者：
G. Pierce;D. Brown;Thomas A. Mustoe, MD, FACS
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作者：
G. Pierce;D. Brown;Thomas A. Mustoe, MD, FACS
血小板衍生生长因子（PDGF-BB 同二聚体）和转化生长因子-β 1 (TGF-β 1) 是有效的伤口愈合激素，可加速切口修复。为了更精确和定量地确定生长因子治疗影响的伤口愈合阶段，我们研究了重组生长因子治疗伤口中的三个连续组织修复过程——炎症细胞流入、细胞内 I 型前胶原 (PC-I) 合成和胶原交联。使用新开发的自动化定量图像分析技术，我们观察到，与 TGF-β1 处理或对照伤口的结果相比，PDGF-BB 在受伤后第一周显着增强了巨噬细胞向伤口的定向迁移，并触发了含 PC-I 的成纤维细胞更早、更持续地流入伤口（第 2 天 p = 0.015；第 21 天 p = 0.007）。相反，自动图像分析显示，与PDGF-BB处理或对照伤口成纤维细胞相比，TGF-β1处理的伤口成纤维细胞的细胞内PC-I蛋白水平增加了近两倍（第4天p = 0.004）。然而，TGF-β1 的影响是短暂的，PDGF-BB 活性的持续时间较长表明影响较晚，可能是在胶原蛋白重塑阶段，这最终是增加伤口强度所必需的。为了解决这种可能性，通过β-氨基丙腈（BAPN）处理抑制生长因子处理伤口中的胶原交联，并分析伤口断裂强度。 PDGF-BB 和 TGF-β 1 均继续增强 BAPN 治疗大鼠的修复，表明它们主要在胶原交联水平上不发挥作用。因此，PDGF-BB似乎增强了伤口愈合的炎症阶段，从而间接触发PC-I合成，而TGF-β1定量地直接增强了PC-I合成，这解释了它们在愈合伤口内的不同活性持续时间。
Platelet-derived growth factor (PDGF-BB homodimer) and transforming growth factor-beta 1 (TGF-beta 1) are potent wound-healing hormones that accelerate incisional repair. To identify more precisely and quantitatively the stage(s) of wound healing influenced by growth-factor therapy, we investigated the three sequential tissue repair processes--inflammatory cell influx, intracellular procollagen type I (PC-I) synthesis, and collagen cross-linking--in recombinant growth factor--treated wounds. Using newly developed automated, quantitative image-analysis techniques, we observed that PDGF-BB markedly augmented the directed migration of macrophages into wounds during the first week after wounding and triggered and earlier and more sustained influx of PC-I--containing fibroblasts into the wound when compared with results in TGF-beta 1-treated or control wounds (p = 0.015 at day 2; p = 0.007 at day 21). In contrast, automated image analysis revealed TGF-beta 1-treated wound fibroblasts had a nearly twofold increase in intracellular levels of PC-I protein when compared with PDGF-BB-treated or control wound fibroblasts (p = 0.004 at day 4). However, the influence of TGF-beta 1 was transient, and the longer duration of PDGF-BB activity suggested a later influence, perhaps on the collagen remodeling phase, which is ultimately required for increased wound strength. To address this possibility, collagen cross-linking in growth factor-treated wounds was inhibited by beta-aminoproprionitrile (BAPN) treatment, and wound breaking strength was analyzed. Both PDGF-BB and TGF-beta 1 continued to enhance repair in BAPN-treated rats, indicating that they do not function primarily at the level of collagen cross-linking. Thus, PDGF-BB appears to enhance the inflammatory phase of wound healing to indirectly trigger PC-I synthesis, whereas TGF-beta 1 quantitatively enhances PC-I synthesis directly, accounting for their differing duration of activities within healing wounds.