Penc S F, Pomahac B, Eriksson E, Detmar M, Gallo R L
Department of Dermatology and Division of Development and Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115-5737, USA.
J Clin Invest. 1999 May;103(9):1329-35. doi: 10.1172/JCI4742.
Proteoglycans (PGs) can influence cell behaviors through binding events mediated by their glycosaminoglycan (GAG) chains. This report demonstrates that chondroitin sulfate B, also known as dermatan sulfate (DS), a major GAG released during the inflammatory phase of wound repair, directly activates cells at the physiologic concentrations of DS found in wounds. Cultured human dermal microvascular endothelial cells exposed to DS responded with rapid nuclear translocation of nuclear factor-kappaB (NF-kappaB), increased expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, and increased ICAM-1 cell surface protein. Heparan sulfate and chondroitin sulfates A and C had no effect on activation of NF-kappaB or induction of ICAM-1. Inhibition of NF-kappaB activation blocked the effect of DS. The increase in cell surface ICAM-1 did not involve TNF-alpha or IL-1 release by endothelial cells, but it was facilitated by autocrine factors whose release was initiated by DS. The ICAM-1-inductive activity of DS was confirmed in vivo. Injection of DS, but not heparin or other chondroitin sulfates, into mice greatly increased circulating levels of soluble ICAM. These data provide evidence that DS, but not other GAGs, initiates a previously unrecognized cell signaling event that can act during the response to injury.
蛋白聚糖（PGs）可通过其糖胺聚糖（GAG）链介导的结合事件影响细胞行为。本报告表明，硫酸软骨素B，也称为硫酸皮肤素（DS），是伤口修复炎症阶段释放的主要GAG，在伤口中发现的生理浓度的DS可直接激活细胞。暴露于DS的培养的人真皮微血管内皮细胞会出现核因子-κB（NF-κB）迅速核转位、细胞间黏附分子-1（ICAM-1）mRNA表达增加以及ICAM-1细胞表面蛋白增加。硫酸乙酰肝素以及硫酸软骨素A和C对NF-κB的激活或ICAM-1的诱导没有影响。抑制NF-κB激活可阻断DS的作用。细胞表面ICAM-1的增加不涉及内皮细胞释放肿瘤坏死因子-α或白细胞介素-1，但由DS引发释放的自分泌因子促进了这种增加。DS的ICAM-1诱导活性在体内得到证实。向小鼠注射DS而非肝素或其他硫酸软骨素，可大大提高循环中可溶性ICAM的水平。这些数据提供了证据，表明DS而非其他GAG引发了一种先前未被认识的细胞信号事件，该事件可在对损伤的反应中发挥作用。
