Patel K D, Lorant E, Jones D A, Prescott M, McIntyre T M, Zimmerman G A
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah School of Medicine, Salt Lake City 84112.
Behring Inst Mitt. 1993 Aug(92):144-64.
The interaction of blood leukocytes with the endothelium of post-capillary venules and other vessels involves regulated expression of molecules on both the endothelial cell (EC) and the leukocyte. This is true for each of the major classes of leukocytes, including lymphocytes, monocytes, and granulocytes. Interaction of polymorphonuclear leukocytes (PMNs), a particular subset of granulocytes, with cultured human endothelium illustrates this concept and also illustrates the diversity of structure, mechanisms of expression, and mechanisms of action of the molecules involved. One group of molecules binds, or "tethers", the PMN to the EC without requiring PMN activation; P-selectin and E-selectin, which are glycoproteins that are expressed by translocation from subcellular granules or synthesis under transcriptional regulation, respectively, are examples. A second group of molecules activates the PMN by binding to signal-transducing receptors. Platelet-activating Factor (PAF), a biologically-active phospholipid, is an example of this class. Its production is controlled by regulation of synthetic enzymes and is induced rapidly (minutes) when EC are appropriately stimulated. PAF is translocated to the EC surface, where it mediates juxtacrine activation of PMNs by binding to a "7 membrane-spanning" receptor. One consequence of juxtacrine activation of PMNs by PAF is functional upregulation of CD11/CD18 integrins on the PMN. These integrins bind to counterreceptors on the EC, enhancing the avidity of adhesion over that provided by P-selectin alone. Thus, combinations of tethering and signaling molecules regulate PMN adhesive interactions with EC. Combinations of such molecules also regulate other functional responses of the PMNs that are important in inflammation. The time-dependent expression of different patterns of tethering and signaling molecules by EC provides a general mechanism for differential adhesion and activation of different classes leukocytes in acute and subacute inflammation.
血液白细胞与毛细血管后微静脉及其他血管内皮之间的相互作用涉及内皮细胞（EC）和白细胞上分子的调控表达。对于包括淋巴细胞、单核细胞和粒细胞在内的每一类主要白细胞而言都是如此。多形核白细胞（PMN）作为粒细胞的一个特定亚群，与培养的人内皮细胞的相互作用阐释了这一概念，同时也说明了所涉及分子的结构多样性、表达机制及作用机制。一类分子可将PMN“系留”于EC而无需PMN激活；P-选择素和E-选择素就是例子，它们分别是通过从亚细胞颗粒转位表达或在转录调控下合成的糖蛋白。另一类分子通过与信号转导受体结合来激活PMN。血小板活化因子（PAF），一种生物活性磷脂，就是这类分子的一个例子。其产生受合成酶调控，当EC受到适当刺激时会迅速（数分钟内）被诱导产生。PAF转位至EC表面，在那里它通过与一种“7次跨膜”受体结合介导PMN的旁分泌激活。PAF对PMN的旁分泌激活的一个后果是PMN上CD11/CD18整合素的功能上调。这些整合素与EC上的反受体结合，增强了黏附亲和力，超过单独由P-选择素提供的黏附力。因此，系留分子和信号分子的组合调节PMN与EC的黏附相互作用。这类分子的组合还调节PMN在炎症中起重要作用的其他功能反应。EC对不同模式的系留分子和信号分子的时间依赖性表达为急性和亚急性炎症中不同类白细胞的差异黏附和激活提供了一种普遍机制。
