Jackson A M, Alexandroff A B, Lappin M B, Esuvaranathan K, James K, Chisholm G D
Department of Surgery (WGH), University of Edinburgh Medical School, U.K.
Immunology. 1994 Jan;81(1):120-6.
The control of integrin activation is fundamental to an understanding of the integrin-dependent cellular adhesion thought to be important for a plethora of basic cellular functions. Using a cell-cell conjugation assay the role of divalent cations in leucocyte function-associated antigen-1 (LFA-1)-dependent cellular adhesion was further investigated. The conjugation of interleukin-2 (IL-2)-activated lymphocytes to tumour cells was found to be energy dependent and required the presence of various divalent cations, removal of which decreased the level of conjugation. Increased concentrations of calcium, magnesium and manganese ions resulted in a corresponding increase in levels of conjugation. This increase in conjugation was LFA-1 dependent. Interestingly, when calcium ions were first removed from LFA-1, treatment of lymphocytes with magnesium and manganese ions gave significantly higher levels of conjugation than in the presence of calcium. Using a simple displacement study, calcium ions were shown to displace magnesium ions resulting in decreased conjugation. However, calcium ions were unable to displace manganese ions for binding to LFA-1. That manganese was exerting its effect via an LFA-1-dependent mechanism was confirmed using monoclonal antibodies to CD11a which negated the increased conjugation frequency due to manganese.
整联蛋白激活的控制对于理解整联蛋白依赖性细胞黏附至关重要，这种黏附被认为对众多基本细胞功能很重要。使用细胞-细胞结合试验进一步研究了二价阳离子在白细胞功能相关抗原-1（LFA-1）依赖性细胞黏附中的作用。发现白细胞介素-2（IL-2）激活的淋巴细胞与肿瘤细胞的结合是能量依赖性的，并且需要各种二价阳离子的存在，去除这些阳离子会降低结合水平。钙、镁和锰离子浓度的增加导致结合水平相应增加。这种结合的增加是LFA-1依赖性的。有趣的是，当首先从LFA-1中去除钙离子时，用镁和锰离子处理淋巴细胞产生的结合水平明显高于存在钙离子时。通过简单的置换研究表明，钙离子会置换镁离子，导致结合减少。然而，钙离子无法置换锰离子以与LFA-1结合。使用针对CD11a的单克隆抗体证实了锰是通过LFA-1依赖性机制发挥作用的，该抗体消除了由于锰导致的结合频率增加。
