Petruzzelli L, Maduzia L, Springer T A
Harvard Medical School, Center for Blood Research, Boston, MA 02115, USA.
J Immunol. 1995 Jul 15;155(2):854-66.
The beta 2-integrin (CD18) family members bind to their ligands subsequent to activation of a number of well defined and diverse signal transduction pathways. The precise molecular changes associated with activation of the integrin family members have remained elusive. Here, we characterize a monoclonal, CBR LFA-1/2, that binds to the beta 2-subunit and is able to mimic activation induced upon stimulation by phorbol esters. The Ab induces binding of the LFA-1-expressing cell line, JY, to ICAM-1 (CD54) and ICAM-3 (CD50). Activation of binding by this Ab is independent of Fc interactions and does not occur through cross-linking at the cell surface, because the Fab fragment of the Ab is able to modulate the same effect. Stimulation of neutrophils with CBR LFA-1/2 induces binding to ICAM-1 through activation of both LFA-1 and Mac-1. Activation of Mac-1 by CBR LFA-1/2 was further confirmed by stimulation of neutrophil binding to fibrinogen, a ligand for Mac-1. CBR LFA-1/2 lowers by 10-fold the concentration of Mg2+ required to achieve maximal binding of LFA-1 to ICAM-1. It therefore appears that CBR LFA-1/2 induces a conformational change that directly increases the avidity of beta 2-integrins for ligands.
β2整合素（CD18）家族成员在多种明确且多样的信号转导途径激活后与其配体结合。与整合素家族成员激活相关的精确分子变化一直难以捉摸。在此，我们鉴定了一种单克隆抗体CBR LFA - 1/2，它与β2亚基结合，并能够模拟佛波酯刺激诱导的激活。该抗体诱导表达LFA - 1的细胞系JY与细胞间黏附分子-1（ICAM - 1，CD54）和ICAM - 3（CD50）结合。此抗体诱导的结合激活不依赖于Fc相互作用，也不是通过细胞表面交联发生的，因为该抗体的Fab片段能够调节相同的效应。用CBR LFA - 1/2刺激中性粒细胞通过激活LFA - 1和Mac - 1诱导其与ICAM - 1结合。中性粒细胞与纤维蛋白原（Mac - 1的一种配体）结合的刺激进一步证实了CBR LFA - 1/2对Mac - 1的激活。CBR LFA - 1/2将实现LFA - 1与ICAM - 1最大结合所需的Mg2+浓度降低了10倍。因此，似乎CBR LFA - 1/2诱导了一种构象变化，直接增加了β2整合素对配体的亲和力。
