Stewart M P, Cabanas C, Hogg N
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, UK.
J Immunol. 1996 Mar 1;156(5):1810-7.
Many leukocyte integrins require activation before they can adhere to their ligands. For example, stimulation of T cells enables the integrin LFA-1 to bind to ligand. This study compares two well known protocols for inducing T cell LFA-1 mediated adhesion to intercellular adhesion molecule-1 (ICAM)-1. We how that treatment with high concentrations of the divalent cation Mg2+ induces a high affinity state of LFA-1, which is reflected in the binding of soluble ICAM-1 and correlates with the expression of the epitope recognized by mAb 24. The second stimulation protocol with the phorbol ester phorbol-12,13-dibutyrate (PDBu) does not induce a high affinity state of LFA-1, and in this situation, adhesion is dependent on cell spreading and intracellular events involving protein kinase C, [Ca2+]i, and actin polymerization. These low affinity LFA-1 receptors are responsible for the initial contact with immobilized ligand because, unlike the Mg2+-stimulated receptors, adhesion is not blocked by soluble ICAM-1. Finally, we used a third method of inducing LFA-1-mediated adhesion by stimulation of T cells through the TCR/CD3 complex. This procedure, which is considered to be a more physiologic trigger for LFA-1 activation, resembles the phorbol ester protocol in that high affinity LFA-1 receptors are not induced and cell adhesion depends on involvement of the cytoskeleton and cell spreading.
许多白细胞整合素在能够黏附其配体之前需要激活。例如，T细胞的刺激能使整合素淋巴细胞功能相关抗原-1（LFA-1）与配体结合。本研究比较了两种诱导T细胞LFA-1介导的与细胞间黏附分子-1（ICAM-1）黏附的著名方案。我们发现，用高浓度的二价阳离子Mg2+处理可诱导LFA-1处于高亲和力状态，这反映在可溶性ICAM-1的结合上，并与单克隆抗体24识别的表位表达相关。用佛波酯佛波醇-12,13-二丁酸酯（PDBu）进行的第二种刺激方案不会诱导LFA-1处于高亲和力状态，在这种情况下，黏附依赖于细胞铺展以及涉及蛋白激酶C、细胞内钙离子浓度（[Ca2+]i）和肌动蛋白聚合的细胞内事件。这些低亲和力的LFA-1受体负责与固定化配体的初始接触，因为与Mg2+刺激的受体不同，可溶性ICAM-1不会阻断黏附。最后，我们使用了第三种通过TCR/CD3复合物刺激T细胞来诱导LFA-1介导的黏附的方法。该程序被认为是LFA-1激活的更生理性触发因素，它与佛波酯方案类似，即不会诱导高亲和力的LFA-1受体，细胞黏附依赖于细胞骨架的参与和细胞铺展。
