Center of Infection and Immunity Amsterdam, Academic Medical Center, Meibergdreef 9, Room G2-132, 1105 AZ Amsterdam, The Netherlands.
Infect Immun. 2010 Jan;78(1):115-24. doi: 10.1128/IAI.00949-09. Epub 2009 Nov 9.
CD44 is involved in several immune responses, such as cellular adhesion, migration, proliferation, and activation. Peritonitis is an important cause of sepsis, and Escherichia coli is one of the major pathogens involved therein. We sought to determine the role of CD44 in the host response to E. coli-induced abdominal sepsis and to assess the function of CD44 in the activation of primary peritoneal macrophages by E. coli or lipopolysaccharide (LPS) purified from this bacterium by using wild-type (WT) and CD44 knockout (KO) mice. CD44 KO mice already demonstrated enhanced CXC chemokine levels in peritoneal lavage fluid at 6 h after infection, whereas tumor necrosis factor alpha (TNF-alpha) and interleukin-6 levels were elevated at 20 h postinfection. In line with this, CD44 KO mouse peritoneal macrophages released more TNF-alpha and macrophage inflammatory protein 2 (MIP-2) than did WT cells upon stimulation with E. coli or LPS in the presence of autologous serum. In contrast, plasma TNF-alpha levels were lower in CD44 KO mice and CD44 KO blood leukocytes secreted similar amounts of TNF-alpha and MIP-2 upon ex vivo incubation with E. coli or LPS. The proinflammatory phenotype of CD44 KO macrophages was not associated with an altered expression of inhibitors of Toll-like receptor signaling, whereas it could be partially reversed by addition of WT serum. CD44 deficiency did not impact on leukocyte recruitment into the peritoneal cavity or organ failure. These data suggest that CD44 differentially influences cytokine and chemokine release by different leukocyte subsets.
CD44 参与多种免疫反应，如细胞黏附、迁移、增殖和激活。腹膜炎是脓毒症的重要病因，而大肠杆菌是其中的主要病原体之一。我们试图确定 CD44 在宿主对大肠杆菌诱导的腹腔感染的反应中的作用，并通过使用野生型（WT）和 CD44 敲除（KO）小鼠来评估 CD44 在大肠杆菌或从该细菌中纯化的脂多糖（LPS）激活原代腹腔巨噬细胞中的作用。CD44 KO 小鼠在感染后 6 小时已经显示出腹腔灌洗液中 CXC 趋化因子水平升高，而肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平在感染后 20 小时升高。与此一致的是，在存在自体血清的情况下，CD44 KO 小鼠的腹腔巨噬细胞在受到大肠杆菌或 LPS 刺激时释放的 TNF-α和巨噬细胞炎症蛋白 2（MIP-2）比 WT 细胞更多。相比之下，在体外与大肠杆菌或 LPS 孵育时，CD44 KO 小鼠的血浆 TNF-α水平较低，并且 CD44 KO 血液白细胞分泌的 TNF-α和 MIP-2 量相似。CD44 KO 巨噬细胞的促炎表型与 Toll 样受体信号转导抑制剂的表达改变无关，而添加 WT 血清可部分逆转这种表型。CD44 缺乏并不影响白细胞向腹腔内的募集或器官衰竭。这些数据表明，CD44 以不同的方式影响不同白细胞亚群的细胞因子和趋化因子释放。
