Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany.
J Immunol. 2013 May 1;190(9):4451-7. doi: 10.4049/jimmunol.1203179.
Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. In this review, we discuss the different signaling pathways leading to the change of integrin adhesiveness in neutrophils, monocytes, and lymphocytes. We thereby focus on the importance of integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration, as each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. Additionally, we discuss endogenous mechanisms that balance and counteract integrin activation and limit leukocyte recruitment at the site of inflammation. Further insight into these complex mechanisms may provide new approaches for developing new anti-inflammatory therapies.
整合素被认为是白细胞募集的关键参与者。整合素功能障碍会导致严重的疾病模式,其特征是无法对抗病原体。尽管炎症反应对宿主防御是有益且必要的,但必须控制这些反应,以防止组织破坏和有害的后遗症。在这篇综述中,我们讨论了导致中性粒细胞、单核细胞和淋巴细胞整合素黏附性改变的不同信号通路。我们因此重点关注整合素激活对于白细胞募集级联反应的不同步骤的重要性,包括滚动、黏附、黏附后强化、血管内爬行和迁移,因为每个步骤都需要一组特定的整合素分子的正常功能,这些分子必须被特异性激活。此外,我们还讨论了平衡和抵消整合素激活并限制炎症部位白细胞募集的内源性机制。进一步深入了解这些复杂的机制可能为开发新的抗炎治疗方法提供新的途径。