MODULATION OF LYMPHOCYTE MITOGEN RESPONSES BY COCULTURED FIBROBLASTS
MODULATION OF LYMPHOCYTE MITOGEN RESPONSES BY COCULTURED FIBROBLASTS
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DOI：
10.1016/0008-8749(81)90016-2
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发表时间：
1981-01-01
影响因子：
4.3
通讯作者：
KORN, JH
中科院分区：
文献类型：
--
作者：
KORN, JH
体内免疫反应发生在富含成纤维细胞（FB）和其他结缔组织细胞的环境中。在体外微培养系统中检测了FB可能影响单核细胞对有丝分裂原的增殖反应的可能性。将人外周血单核细胞（MC）与丝裂霉素c处理的[人]FB在植物血凝素（PHA）或欧陆丝裂原（PWM）存在下共培养。共培养FB （FB:MC比例为1:10 ~ 1:10）抑制了MC对PHA的反应（高达35%），但对PWM反应没有显著影响。与单独培养的MC或FB相比，FB和MC共培养的前列腺素E2浓度增加了10至30倍。用吲哚美辛或甲氧胺酸抑制前列腺素合成可显著逆转fb介导的淋巴细胞PHA抑制反应。前列腺素依赖的FB抑制淋巴细胞PHA反应仅在MC暴露于PHA开始时开始FB:MC共培养时可见。PHA培养24 h后，在MC中加入FB，未见效果。在48或66 h时添加前列腺素可增强淋巴细胞对PHA的增殖反应。因此，在FB和MC共培养中，MC对PHA的反应性可能部分通过FB前列腺素代谢的改变而受到影响。FB和MC之间的相互作用可能在炎症病变的免疫反应调节中起重要作用。
Immunological reactions in vivo occur in an environment rich in fibroblasts (FB) and other connective tissue cells. The possibility that FB might affect mononuclear cell proliferative responses to mitogens in vitro was examined in a microculture system. Human peripheral blood mononuclear cells (MC) were cocultured with mitomycin C-treated [human] FB in the presence of phytohemagglutinin (PHA) or pokeweed mitogen (PWM). Cocultured FB (at a 1:100 to 1:10 FB:MC ratio) suppressed the response of MC to PHA (by as much as 35%) but did not significantly affect PWM responses. Cocultures of FB and MC were characterized by 10- to 30-fold increases in prostaglandin E2 concentrations compared to MC or FB cultured alone. Inhibition of prostaglandin synthesis with indomethacin or mefenamic acid significantly reversed the FB-mediated suppression of lymphocyte PHA responses. Prostaglandin-dependent FB suppression of lymphocyte PHA responses was seen only when FB:MC coculture was initiated at the onset of exposure of MC to PHA. When FB were added to MC after 24 h of culture with PHA, no effect was seen. Addition at 48 or 66 h resulted in prostaglandin-independent enhancement of lymphocyte proliterative responses to PHA. Thus, in cocultures of FB and MC, MC reactivity to PHA may be influenced in part via alterations in FB prostaglandin metabolism. The interaction between FB and MC may be important in the modulation of immune responses in inflammatory lesions.