Activated human B lymphocytes express cyclooxygenase-2 and cyclooxygenase inhibitors attenuate antibody production
Activated human B lymphocytes express cyclooxygenase-2 and cyclooxygenase inhibitors attenuate antibody production
复制标题
DOI：
10.4049/jimmunol.174.5.2619
复制
发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Phipps, RP
中科院分区：
文献类型：
--
作者：
Ryan, EP;Pollack, SJ;Phipps, RP
非甾体类抗炎药 (NSAID) 广泛用于治疗炎症性疾病，并针对负责 PG 产生的环氧合酶 1 和 2（Cox-1、Cox-2）。较新的 Cox-2 选择性药物已被大量用于缓解炎症。关于这些药物是否影响人类 B 淋巴细胞及其产生抗体的能力，人们知之甚少。我们在此报道，激活的人B细胞不仅高度表达Cox-2并产生PG，而且NSAID吲哚美辛和Cox-2选择性药物在体外深刻抑制人B细胞产生IgG和IgM的能力。人血 B 细胞高度表达 Cox-2 mRNA 和蛋白质，并在 CD40L、pansorbin 或 CD40L 加 BCR 结合激活后产生 PG。免疫组织化学显示，人扁桃体 B 细胞也高度表达 Cox-2。 Cox 抑制药物会适度影响纯化的 B 细胞增殖，但会显着减少抗体的产生。全血在刺激后产生 IgM 和 IgG 的能力也受到强烈抑制。与正常同窝对照小鼠相比，Cox-2 敲除小鼠的 IgM 含量减少了 64%，IgG 含量减少了 35%，这支持了 Cox-2 在 B 淋巴细胞抗体产生中发挥重要作用。这些发现支持 NSAID 和新的 Cox-2 选择性药物有一个意想不到的靶标，即 B 细胞，并能减弱人体的抗体产生。因此，使用非甾体抗炎药可能会影响自身免疫性疾病中自身抗体的产生，并可能抑制针对抗原攻击/疫苗接种的体液免疫。
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of inflammatory diseases and target cyclooxygenases 1 and 2 (Cox-1, Cox-2) that are responsible for PG production. Newer Cox-2-selective drugs have been heavily prescribed to quench inflammation. Little is known about whether or not these drugs influence human B lymphocytes and their ability to produce Ab. We report herein that activated human B cells not only highly express Cox-2 and produce PGs, but that the NSAID indomethacin and Cox-2-selective drugs profoundly inhibit the ability of human B cells to produce IgG and IgM in vitro. Human blood B cells highly express Cox-2 mRNA and protein and produce PGs after activation with CD40L, pansorbin, or CD40L plus BCR engagement. Cox-2 is also highly expressed by human tonsil B cells, as shown by immunohistochemistry. Cox-inhibiting drugs modestly affect purified B cell proliferation but profoundly reduce Ab production. The ability of whole blood to produce IgM and IgG following stimulation is also strongly inhibited. In support that Cox-2 plays a seminal role in B lymphocyte Ab production, Cox-2 knockout mice have 64% less IgM and 35% less IgG than normal littermate controls. These findings support that NSAIDs and the new Cox-2-selective drugs have an unsuspected target, the B cell, and attenuate Ab production in humans. Use of NSAIDs may therefore influence autoantibody production in autoimmune diseases and may dampen humoral immunity in response to antigenic challenge/vaccination.