Regulation of mast cell migration by TH1 and TH2 cytokines:: Identification of tumour necrosis factor-α and interleukin-4 as mast cell chemotaxins
Regulation of mast cell migration by TH1 and TH2 cytokines:: Identification of tumour necrosis factor-α and interleukin-4 as mast cell chemotaxins
复制标题
DOI：
10.1111/j.0300-9475.2004.01397.x
复制
发表时间：
2004-03-01
影响因子：
3.7
通讯作者：
Nilsson, G
中科院分区：
文献类型：
--
作者：
Olsson, N;Taub, DD;Nilsson, G
肥大细胞在许多炎症疾病中扮演中枢效应细胞和调节细胞的角色，包括辅助性T- h1介导的炎症，如自身免疫和T- h2介导的炎症，如过敏和寄生虫感染。肥大细胞介导的炎症的一个特征是肥大细胞在炎症组织中的积累。在这些炎症中调节肥大细胞募集的因素仍未完全确定。我们研究了T-H1和t - h2分泌的细胞因子介导肥大细胞迁移的效力。使用人肥大细胞系（HMC-1）作为应答细胞，对6种不同T-H1和T-H2克隆的上清液进行了肥大细胞趋化活性测试。所有六个克隆都产生了诱导肥大细胞迁移的因子。使用针对多种细胞因子的阻断抗体，我们发现抗肿瘤坏死因子- α (anti- tnf - α)减少了肥大细胞向T-H1克隆上清的迁移。相比之下，T-H2克隆分泌的主要肥大细胞化学引诱剂是白细胞介素-4 （IL-4）和IL-8。利用重组IL-4、IL-8和tnf - α证实了这些细胞因子作为肥大细胞化学引诱剂的效力。我们的研究结果表明，在t - h1介导的炎症中，tnf - α可能参与肥大细胞的募集，而IL-4和IL-8可能在t - h2介导的炎症中发挥类似的作用。
Mast cells act as central effector and regulatory cells in many inflammatory disorders, including T helper 1 (T-H1)-mediated inflammations such as autoimmunity and T-H2-mediated inflammations such as allergy and parasite infections. One characteristic for mast cell-mediated inflammations is the accumulation of mast cells in the inflamed tissue. The factors regulating mast cell recruitment in these inflammations are still not fully characterized. We have investigated the potency of T-H1- and T-H2-secreted cytokines to mediate mast cell migration. Supernatants from six different T-H1 and T-H2 clones were tested for mast cell-chemotactic activity using the human mast cell line (HMC-1) as a responder cell. All six clones produced factors that induced mast cell migration. Using blocking antibodies to a broad range of cytokines, we found that anti-tumour necrosis factor-alpha (anti-TNF-alpha) reduced the migration of mast cells to supernatants from T-H1 clones. In contrast, the main mast cell chemoattractants secreted by T-H2 clones were found to be interleukin-4 (IL-4) and IL-8. The potency of these cytokines to act as mast cell chemoattractants was confirmed by using recombinant IL-4, IL-8 and TNF-alpha. Our results suggest that TNF-alpha can be involved in the recruitment of mast cells in T-H1-mediated inflammations, whereas IL-4 and IL-8 might play a similar role in T-H2-mediated inflammations.