Cell migration in the immune system: the evolving inter-related roles of adhesion molecules and proteinases.
Cell migration in the immune system: the evolving inter-related roles of adhesion molecules and proteinases.
复制标题
DOI：
10.1155/2000/79045
复制
发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Graesser, D
中科院分区：
文献类型：
--
作者：
Madri, J A;Graesser, D
炎症期间白细胞渗入血管周围组织，淋巴细胞归巢至淋巴器官，包括与血管内皮细胞的瞬时黏附，随后通过内皮细胞(EC)层的迁移，并在组织部位建立一段时间的驻留。在这些过程中，在跨内皮细胞迁移之前，白细胞会多次附着和脱离血管衬里的内皮细胞。迁移的白细胞在到达血管周围组织的途中必须穿过内皮下基底膜，并利用被称为基质金属蛋白酶的酶在基底膜的细胞外基质成分中选择性地夹住。本文就白细胞与内皮细胞的黏附、白细胞黏附受体介导的基质金属蛋白酶的诱导以及利用这些基质金属蛋白酶促进白细胞侵袭组织的能力之间的联系进行综述。具有侵袭性表型的白细胞表达高水平的MMPs，MMPs的表达增强了这些细胞的迁移和侵袭性。此外，MMPs还可被淋巴细胞用来对黏附受体和膜结合细胞因子等分子进行蛋白水解性切割，提高它们在免疫应答中的效率。白细胞黏附受体的参与可以调节侵袭性白细胞的黏附(整合素亲和力和表达的调节)、合成(蛋白酶的诱导和激活)和表面组织(蛋白分解复合体的聚集)行为。阐明这些途径将有助于更好地理解调控机制，以便在炎症和自身免疫领域开发合理的治疗方法。
Leukocyte extravasation into perivascular tissue during inflammation and lymphocyte homing to lymphoid organs involve transient adhesion to the vessel endothelium, followed by transmigration through the endothelial cell (EC) layer and establishment of residency at the tissue site for a period of time. In these processes, leukocytes undergo multiple attachments to, and detachments from, the vessel-lining endothelial cells, prior to transendothelial cell migration. Transmigrating leukocytes must traverse a subendothelial basement membrane en route to perivascular tissues and utilize enzymes known as matrix metalloproteinases to make selective clips in the extracellular matrix components of the basement membrane. This review will focus on the evidence for a link between adhesion of leukocytes to endothelial cells, the induction of matrix metalloproteinases mediated by engagement of adhesion receptors on leukocytes, and the ability to utilize these matrix metalloproteinases to facilitate leukocyte invasion of tissues. Leukocytes with invasive phenotypes express high levels of MMPs, and expression of MMPs enhances the migratory and invasive properties of these cells. Furthermore, MMPs may be used by lymphocytes to proteolytically cleave molecules such as adhesion receptors and membrane bound cytokines, increasing their efficiency in the immune response. Engagement of leukocyte adhesion receptors may modulate adhesive (modulation of integrin affinities and expression), synthetic (proteinase induction and activation), and surface organization (clustering of proteolytic complexes) behaviors of invasive leukocytes. Elucidation of these pathways will lead to better understanding of controlling mechanisms in order to develop rational therapeutic approaches in the areas of inflammation and autoimmunity.