Hartmann K, Henz B M, Krüger-Krasagakes S, Köhl J, Burger R, Guhl S, Haase I, Lippert U, Zuberbier T
Department of Dermatology, Virchow Clinics, Humboldt University of Berlin, Germany.
Blood. 1997 Apr 15;89(8):2863-70.
The factors that control migration of mast cells to sites of inflammation and tissue repair remain largely undefined. Whereas several recent studies have described chemotactic factors that induce migration of murine mast cells, only stem cell factor (SCF) is known to induce migration of human mast cells. We report here that the anaphylatoxins C3a and C5a are chemotactic factors for the human mast cell line HMC-1, human cord blood-derived mast cells (CBMC) and cutaneous mast cells in vitro. The presence of an extracellular matrix protein, laminin, was required for chemotaxis in response to complement peptides. Migration of mast cells towards C3a and C5a was dose-dependent, peaking at 1 microg/mL (100 nmol/L), and was inhibited by specific antibodies. Pretreatment with pertussis toxin inhibited the anaphylatoxin-mediated migration of HMC-1 cells, indicating that Gi proteins are involved in complement-activated signal transduction pathways in human mast cells. Both C3a and C5a also induced a rapid and transient mobilization of intracellular free calcium ([Ca2+]i) in HMC-1 cells. Besides SCF, other chemotactic factors tested, such as interleukin-3, nerve growth factor, transforming growth factor beta, RANTES (regulated upon activation, normal Tcell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, failed to stimulate migration of human mast cells. In summary, these findings indicate that C3a and C5a serve as chemotaxins for human mast cells. Anaphylatoxin-mediated recruitment of mast cells might play an important role in hypersensitivity and inflammatory processes.
控制肥大细胞迁移至炎症和组织修复部位的因素在很大程度上仍不明确。尽管最近有几项研究描述了诱导小鼠肥大细胞迁移的趋化因子，但已知只有干细胞因子（SCF）能诱导人肥大细胞迁移。我们在此报告，过敏毒素C3a和C5a是体外人肥大细胞系HMC-1、人脐带血来源的肥大细胞（CBMC）和皮肤肥大细胞的趋化因子。响应补体肽的趋化作用需要细胞外基质蛋白层粘连蛋白的存在。肥大细胞向C3a和C5a的迁移呈剂量依赖性，在1微克/毫升（100纳摩尔/升）时达到峰值，并被特异性抗体抑制。百日咳毒素预处理可抑制过敏毒素介导的HMC-1细胞迁移，表明Gi蛋白参与人肥大细胞中补体激活的信号转导途径。C3a和C5a还能在HMC-1细胞中诱导细胞内游离钙（[Ca2+]i）的快速短暂动员。除了SCF外，所测试的其他趋化因子，如白细胞介素-3、神经生长因子、转化生长因子β、调节激活正常T细胞表达和分泌的趋化因子（RANTES）、单核细胞趋化蛋白-1（MCP-1）、MCP-2、MCP-3、巨噬细胞炎性蛋白-1α（MIP-1α）和MIP-1β，均未能刺激人肥大细胞迁移。总之，这些发现表明C3a和C5a是人肥大细胞的趋化因子。过敏毒素介导的肥大细胞募集可能在超敏反应和炎症过程中起重要作用。
