哮喘联盟

    背景：组织嗜酸性粒细胞增多是包括哮喘在内的过敏性疾病和Th2型免疫反应的标志之一。已知粘附分子参与了过敏性炎症病灶中嗜酸性粒细胞的聚集，导致嗜酸性粒细胞的活化。有研究发现哮喘患者体内可溶性粘附分子增加，但是其病理生理学重要性尚待阐明。
    方法：纯化外周血嗜酸性粒细胞，采用体外系统研究可溶性血管细胞粘附分子-1（sVCAM-1）对嗜酸性粒细胞迁移的影响。
    结果：sVCAM-1（1-10 mug/ml）能诱导嗜酸性粒细胞的趋化性，而不是化学激活，且这种趋化为浓度依赖性。此外，sVCAM-1能诱导细胞形态的改变和肌动蛋白的聚合，这些都是细胞运动的必要条件。使用极迟抗原（VLA）-4中和抗体和信号转导抑制物处理后，显示sVCAM-1诱导的趋化性是通过配体依赖的酪氨酸激酶Src、p38丝裂原活化蛋白激酶（MAPK）及细胞外信号调节激酶（ERK）MAPK的活化介导的。基于微球的多重化分析显示，这些信号分子出现快速磷酸化。
    结论：该研究结果为体内可溶性粘附分子sVCAM-1增加可能导致嗜酸性粒细胞性炎症反应增强的结论增加了证据。

（苏楠 审校）
Ueki S, et al. Allergy. 2009 Feb 10. [Epub ahead of print]

Soluble vascular cell adhesion molecule-1 induces human eosinophil migration.

Background: Tissue eosinophilia is one of the hallmarks of allergic diseases and Th2-type immune responses including asthma. Adhesion molecules are known to play an important role in the accumulation of eosinophils in allergic inflammatory foci, and they contribute to eosinophil activation. Elevated levels of the soluble forms of adhesion molecules in the body fluid of asthmatic patients have been observed, although their pathophysiological significance remains to be fully elucidated.
Methods: Peripheral blood eosinophils were purified, and the effect of soluble vascular cell adhesion molecule-1 (sVCAM-1) on eosinophil migration was investigated using in vitro systems.
Results: We found that sVCAM-1 (1 to 10 mug/ml) induced eosinophil chemotaxis, rather than chemokinesis, in a concentration-dependent fashion. In addition, sVCAM-1 induced cell shape change and actin polymerization, which are necessary for cell movement. Manipulations with very late antigen (VLA)-4-neutralizing antibody and signal inhibitors indicated that the sVCAM-1-induced chemotaxis was mediated through ligand-dependent activation of tyrosine kinase Src, p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase (ERK) MAPK. Rapid phosphorylation of these signaling molecules was observed using a bead-based multiplex assay.
Conclusion: Our results raise the possibility of sVCAM-1 in the fluid phase as a significant contributor to the heightened eosinophilic inflammatory response.