Kanno H, Yasunaga Y, Iuchi K, Yamauchi S, Tatekawa T, Sugiyama H, Aozasa K
Department of Pathology, Osaka University Medical School, Suita, Japan.
Lab Invest. 1996 Aug;75(2):167-73.
Malignant lymphomas frequently develop in the pleural cavity of the patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PAL are diffuse large cell lymphoma of B cell type that contain Epstein-Barr virus DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Because PAL develop in the sites of chronic inflammation, inflammatory cytokines might be involved in the lymphomagenesis. To address this point, we examined the regulation of the growth of OPL by human IL-6. Human recombinant IL-6 enhanced the growth rate of OPL. OPL-1 responded to recombinant IL-6 by growing faster even at concentrations of less than 0.1 ng/ml, whereas OPL-2 required higher concentrations of recombinant IL-6. OPL expressed IL-6 receptor mRNA detectable by reverse transcriptase PCR analysis and IL-6 receptor on cell surface by flow cytometric analysis, using anti-IL-6 receptor antibodies. On the other hand, only OPL-1 showed expression of IL-6 mRNA, which was detectable only by reverse transcriptase PCR, and secreted IL-6 protein into the culture media. The culture supernatant of OPL-1 exhibited growth-enhancing effects on OPL-1 and OPL-2. The addition of anti-IL-6 antibodies to the cultures inhibited the growth of OPL-1 but not OPL-2. OPL-2 did not secrete IL-6 protein into the media, and the culture supernatant from OPL-2 did not enhance growth of OPL-2. These findings suggest the involvement of IL-6 in the growth regulation of OPL, i.e., an autocrine mechanism of IL-6-related proliferation in OPL-1 and a paracrine mechanism in OPL-2. IL-6 locally produced in chronic pyothorax might also promote the development of PAL.
恶性淋巴瘤常发生于长期脓胸患者的胸腔内。因此，已提出“脓胸相关淋巴瘤（PAL）”这一术语来描述此类肿瘤。大多数PAL是含有爱泼斯坦 - 巴尔病毒DNA的B细胞型弥漫性大细胞淋巴瘤。我们从PAL病例的活检标本中建立了两个淋巴瘤细胞系，OPL - 1和OPL - 2。由于PAL发生于慢性炎症部位，炎性细胞因子可能参与淋巴瘤的发生。为阐明这一点，我们研究了人IL - 6对OPL生长的调节作用。人重组IL - 6提高了OPL的生长速率。OPL - 1对重组IL - 6反应敏感，即使在浓度低于0.1 ng/ml时生长也加快，而OPL - 2则需要更高浓度的重组IL - 6。通过逆转录酶PCR分析可检测到OPL表达IL - 6受体mRNA，利用抗IL - 6受体抗体通过流式细胞术分析可检测到细胞表面的IL - 6受体。另一方面，只有OPL - 1显示出IL - 6 mRNA的表达，仅通过逆转录酶PCR可检测到，并且OPL - 1将IL - 6蛋白分泌到培养基中。OPL - 1的培养上清液对OPL - 1和OPL - 2均表现出生长促进作用。向培养物中添加抗IL - 6抗体可抑制OPL - 1的生长，但不抑制OPL - 2的生长。OPL - 2不向培养基中分泌IL - 6蛋白，OPL - 2的培养上清液也不促进OPL - 2的生长。这些发现提示IL - 6参与了OPL的生长调节，即OPL - 1中存在IL - 6相关增殖的自分泌机制，而在OPL - 2中存在旁分泌机制。慢性脓胸中局部产生的IL - 6也可能促进PAL的发生。
