Sehmi R, Baatjes A J, Denburg J A
Department of Medicine, HSC-3V46, McMaster University, 1200 Main St West, Hamilton, ON L8N 3Z5, Canada.
Curr Drug Targets Inflamm Allergy. 2003 Dec;2(4):271-8. doi: 10.2174/1568010033484007.
Eosinophilic infiltration is a cardinal feature of allergic inflammation; based upon its biological actions, the eosinophil has assumed the role as the principal inflammatory cell in asthma. In assessing the mechanisms by which eosinophils are recruited to sites of inflammation, a sizeable body of evidence exists supporting the proposal that expansion of hemopoietic compartments in the bone marrow stimulates an increased turnover and traffic of mature eosinophils to the site of allergic inflammation. In addition, recent findings point to the possible egress and traffic of primitive progenitor cells to the site of inflammation where in-situ differentiation may provide a continued supply of pro-inflammatory cells. In the present article, we will review the evidence for these findings, and discuss the rationale for targeting hemopoiesis and migrational pathways of hemopoietic cells in the treatment of allergic disease. In this context, we will discuss the effect of corticosteroid treatment on hemopoietic mechanisms; the effects of therapies that inhibit the actions of cysteinyl leukotrienes (CysLTs); the effects of in vivo blockade of the eosinophil-active cytokine, interleukin (IL)-5; and, the effects of antihistamines on hemopoiesis. In addition, we will address the potential role that small molecular weight chemokine receptor antagonists may play in modulating progenitor cell trafficking to tissue sites of inflammation.
嗜酸性粒细胞浸润是过敏性炎症的主要特征;基于其生物学作用,嗜酸性粒细胞已成为哮喘中的主要炎症细胞。在评估嗜酸性粒细胞被募集到炎症部位的机制时,有大量证据支持以下观点:骨髓中造血细胞区室的扩张会刺激成熟嗜酸性粒细胞的更新增加并向过敏性炎症部位迁移。此外,最近的研究结果表明,原始祖细胞可能会向外迁移并到达炎症部位,在那里原位分化可能会持续提供促炎细胞。在本文中,我们将回顾这些研究结果的证据,并讨论在过敏性疾病治疗中针对造血作用和造血细胞迁移途径的基本原理。在此背景下,我们将讨论皮质类固醇治疗对造血机制的影响;抑制半胱氨酰白三烯(CysLTs)作用的疗法的效果;体内阻断嗜酸性粒细胞活性细胞因子白细胞介素(IL)-5的效果;以及抗组胺药对造血作用的影响。此外,我们将探讨小分子趋化因子受体拮抗剂在调节祖细胞向炎症组织部位迁移中可能发挥的潜在作用。