Soluble mediators from mononuclear cells increase the synthesis of glycosaminoglycan by dermal fibroblast cultures derived from normal subjects and progressive systemic sclerosis patients.
Soluble mediators from mononuclear cells increase the synthesis of glycosaminoglycan by dermal fibroblast cultures derived from normal subjects and progressive systemic sclerosis patients.
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来自单核细胞的可溶性介质增加了来自正常受试者和进行性系统性硬化症患者的真皮成纤维细胞培养物的糖胺聚糖的合成。
DOI：
10.1002/art.1780280214
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发表时间：
1985
影响因子：
--
通讯作者：
Rodnan,GP
中科院分区：
文献类型：
--
作者：
Whiteside,TL;Worrall,JG;Prince,RK;Buckingham,RB;Rodnan,GP
进行性系统性硬化症（PSS）患者的真皮成纤维细胞培养物合成的糖胺聚糖（GAG）是正常培养物的5倍。在成纤维细胞-淋巴细胞相互作用的体外模型中，我们表明活化单核细胞（MNC）的上清液调节GAG合成，通过将融合的成纤维细胞单层与活性上清液制剂孵育后将3 H-葡萄糖胺掺入GAG进行测量。在正常真皮成纤维细胞培养物中，GAG蓄积选择性增加高达18倍。细胞活力不受影响，用上清液处理的培养物中3 H-胸苷摄取和细胞数量受到抑制。与正常真皮成纤维细胞培养物相比，PSS成纤维细胞对MNC上清液的反应仅为GAG增加1-2倍。伴刀豆球蛋白A激活的PSS MNC的上清比正常MNC具有更高的刺激活性。在Sephadex G-10柱上用已耗尽单核细胞的MNC制备的上清液仅具有最低限度的刺激性。GAG刺激性上清液调节GAG的合成，但不调节GAG的降解。在经校准的Sephadex G-100柱上的凝胶过滤表明在50，000和15，000分子量级分中均存在刺激活性。这些活性是胰蛋白酶敏感的，但对热的敏感性不同。活性柱组分还含有白细胞介素-1活性，如测量小鼠胸腺细胞增殖的试验所示。与我们的因子一样，白细胞介素-1制剂增加了正常和PSS真皮成纤维细胞中的GAG。活化的MNC的产物可以调节人皮肤的正常和病理过程。
Dermal fibroblast cultures from patients with progressive systemic sclerosis (PSS) synthesize up to 5 times more glycosaminoglycan (GAG) than normal cultures. In an in vitro model of fibroblast‐lymphocyte interactions, we show that the supernatants of activated mononuclear cells (MNC) modulate GAG synthesis, as measured by the incorporation of3H‐glucosamine into GAG following incubation of the confluent fibroblast monolayers with active supernatant preparations. GAG accumulation was selectively increased up to 18 times in normal dermal fibroblast cultures. Cell viability was not affected, and3H‐thymidine uptake and cell numbers were depressed in cultures treated with the supernatants. In contrast to normal dermal fibroblast cultures, PSS fibroblasts responded to MNC supernatants by only a 1–2‐fold increase in GAG. Supernatants of concanavalin A‐activated PSS MNC had higher stimulatory activity than those of normal MNC. Supernatants made with MNC that had been depleted of monocytes on Sephadex G‐10 columns were only minimally stimulatory. The GAG‐stimulatory supernatants modulated the synthesis, but not the degradation of GAG. Gel filtration on a calibrated Sephadex G‐100 column indicated the presence of stimulatory activity in both the 50,000 and 15,000 molecular weight fractions. These activities were trypsin‐sensitive, but had different susceptibilities to heat. The active column fractions also contained interleukin‐1 activity, as shown in an assay measuring proliferation of mouse thymocytes. Like our factors, interleukin‐1 preparations increased GAG in normal and PSS dermal fibroblasts. Products of activated MNC may modulate normal and pathologic processes in human skin.