Department of Anesthesiology and Intensive Care Medicine, University of Münster, Albert-Schweitzer Strasse 33, Münster, Germany.
J Mol Med (Berl). 2012 Apr;90(4):353-9. doi: 10.1007/s00109-011-0835-2. Epub 2011 Nov 19.
Leukocyte recruitment into tissue forms the basis of immune surveillance and direct immune defense. It proceeds in a cascade-like fashion. The first contact of leukocytes with the endothelium is mediated by selectins and their counter receptors, followed by rolling and integrin-mediated arrest. While rolling, neutrophils collect different inflammatory signals which can activate several signaling pathways leading to leukocyte adhesion to the endothelium and transmigration through the blood vessel wall into the inflamed tissue. Whereas inflammatory reactions are beneficial and necessary for host defense, they need to be balanced and controlled to prevent harmful consequences and tissue destruction. In this article, we discuss the different signaling pathways that ensure rapid and efficient integrin activation on leukocytes. In addition, we report on a recently identified novel endogenous mechanism that counteracts and balances integrin activation, thereby limiting leukocyte recruitment and the extent of inflammation. Further investigation of this new mechanism may allow providing new approaches for the development of the next generation of anti-inflammatory drugs.
白细胞向组织内的募集是免疫监视和直接免疫防御的基础。这一过程呈级联式发生。白细胞与血管内皮的最初接触由选择素及其相应受体介导，随后是滚动和整合素介导的黏附。在滚动过程中，中性粒细胞收集不同的炎症信号，这些信号可以激活多种信号通路，导致白细胞与内皮细胞黏附，并穿过血管壁进入炎症组织。虽然炎症反应对宿主防御有益且是必需的，但需要加以平衡和控制，以防止产生有害后果和组织破坏。本文讨论了确保白细胞上整合素快速有效激活的不同信号通路。此外，我们还报告了一种新发现的内源性拮抗和平衡整合素激活的机制，从而限制了白细胞募集和炎症的程度。对这一新机制的进一步研究可能为开发新一代抗炎药物提供新的方法。
