Bone marrow stromal cells inhibit mast cell function via a COX2-dependent mechanism.
Bone marrow stromal cells inhibit mast cell function via a COX2-dependent mechanism.
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DOI：
10.1111/j.1365-2222.2010.03685.x
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Mezey E
中科院分区：
文献类型：
--
作者：
Brown JM;Nemeth K;Kushnir-Sukhov NM;Metcalfe DD;Mezey E
肥大细胞（MC）在诱导过敏性炎症（如哮喘）中起核心作用，并导致某些自身免疫性疾病（如类风湿性关节炎）的严重程度。因此，肥大细胞代表了一种重要的炎症细胞，并且是一种抵抗改变其在疾病中的作用的治疗尝试的细胞。由于骨髓来源的基质细胞（BMSC，也称为间充质干细胞或MSC）已被报道可以改变体内过敏性炎症，我们选择研究小鼠BMSC和小鼠骨髓来源的MCs之间的相互作用。MC脱粒，细胞因子的产生和趋化性进行了评价，在体外与BMSCs的细胞接触或transwell共培养。此外，在被动皮肤过敏反应模型和腹膜脱粒试验中，在体内评估了BMSC给药后MC脱粒。通过使用COX 1、COX 2、一氧化氮、吲哚胺2，3-双加氧酶、EP 1 -4受体、TGF-β和IL-10的抑制剂或抗体来确定BMSCs抑制MC的机制。最后，我们利用BMSCs或COX 1、COX 2或EP 1 -4受体缺陷的MC来证实BMSCs抑制MC功能的机制。我们发现BMSCs在体外和体内都能有效地抑制特定的MC功能。当MCs与BMSCs共培养以允许细胞与细胞接触时，BMSCs抑制MC脱粒、促炎细胞因子产生、趋化和趋化。同样，小鼠皮肤或腹腔内的MC脱粒在体内施用BMSC后被抑制。此外，我们发现这些抑制作用依赖于BMSCs中COX 2的上调，并通过激活MC上的EP 4受体而促进。这些观察结果支持了BMSC具有抑制肥大细胞活化的能力的概念，因此可能是治疗MC驱动的炎性疾病的新型基于细胞的治疗方法的基础。
Mast cells (MCs) have a central role in the induction of allergic inflammation, such as seen in asthma, and contribute to the severity of certain autoimmune diseases, such as rheumatoid arthritis. The mast cell thus represents an important inflammatory cell, and one which has resisted therapeutic attempts to alter its role in disease. Because bone marrow-derived stromal cells (BMSC, also known as mesenchymal stem cells or MSCs) have been reported to alter allergic inflammation in vivo, we chose to study the interaction between mouse BMSC and mouse bone marrow derived MCs. MC degranulation, cytokine production and chemotaxis were evaluated in vitro following co-culture with BMSCs either in cell contact or a transwell. In addition, MC degranulation was assessed in vivo following administration of BMSCs in a model of passive cutaneous anaphylaxis and a peritoneal degranulation assay. Mechanisms of MC suppression by BMSCs were determined through use of inhibitors or antibodies to COX1, COX2, nitric oxide, indoleamine 2, 3-dioxygenase, EP1-4 receptors, TGF-β and IL-10. Lastly, we utilized either BMSCs or MCs deficient in COX1, COX2 or EP1-4 receptors to confirm the mechanisms of inhibition of MC function by BMSCs. We discovered that BMSCs will effectively suppress specific MC functions in vitro as well as in vivo. When MCs are cocultured with BMSCs to allow cell-to-cell contact, BMSCs suppressed MC degranulation, proinflammatory cytokine production, chemokinesis and chemotaxis. Similarly, MC degranulation within mouse skin or the peritoneal cavity was suppressed following in vivo administration of BMSCs. Further, we found that these inhibitory effects were dependent on up-regulation of COX2 in BMSCs; and were facilitated through the activation of EP4 receptors on MCs. These observations support the concept that BMSCs have the ability to suppress mast cell activation and therefore could be the basis for a novel cell based therapeutic approach in the treatment of MC driven inflammatory diseases.
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DOI：
10.4049/jimmunol.181.4.2772
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hollins F;Kaur D;Yang W;Cruse G;Saunders R;Sutcliffe A;Berger P;Ito A;Brightling CE;Bradding P
通讯作者：
Bradding P
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0910720107
发表时间：
2010-03-23
影响因子：
11.1
作者：
Nemeth, Krisztian;Keane-Myers, Andrea;Mezey, Eva
通讯作者：
Mezey, Eva
影响因子：
4
作者：
Chen, Lei;Zhang, Wei;Zhao, Robert Chunhua
通讯作者：
Zhao, Robert Chunhua
影响因子：
4.4
作者：
Abdel-Majid, RM;Marshall, JS
通讯作者：
Marshall, JS