Dettke M, Loibner H
Clinic for Blood Group Serology and Transfusion Medicine, University Hospital of Vienna, Austria.
Br J Cancer. 2000 Jan;82(2):441-5. doi: 10.1054/bjoc.1999.0940.
Stimulation of monocytes by interaction of monoclonal antibodies (mAbs) with Fc gamma receptors (FcgammaRs) results in the activation of various monocyte effector functions. In the present investigation we show that the anti-Lewis Y (LeY) anti-tumour mAb ABL 364 and its mouse/human IgG1 chimaera induce both antibody-dependent cellular cytotoxicity (ADCC) and the release of tumour necrosis factor alpha (TNF-alpha) during mixed culture of monocytes with LeY+ SKBR5 breast cancer cells in vitro. Although anti-LeY mAb-mediated TNF-alpha release paralleled ADCC activity, cytokine release required a higher concentration of sensitizing mAb than the induction of cytolysis. The determination of the FcgammaR classes involved in the induction of the distinct effector functions showed that anti-LeY mAb-induced cytolysis was triggered by interaction between anti-LeY mAbs and FcgammaRI. In contrast, mAb-induced TNF-alpha release mainly depended on the activation of monocyte FcgammaRII. Neutralization of TNF-alpha showed no influence on monocyte ADCC activity towards SKBR5 target cells. Our data indicate an independent regulation of anti-LeY mAb induced effector functions of ADCC and TNF-alpha release which seemed to be triggered by activation of different types of FcgammaR.
单克隆抗体（mAb）与Fcγ受体（FcgammaRs）相互作用刺激单核细胞，会导致各种单核细胞效应功能的激活。在本研究中，我们发现抗Lewis Y（LeY）抗肿瘤单克隆抗体ABL 364及其小鼠/人IgG1嵌合体在体外单核细胞与LeY + SKBR5乳腺癌细胞混合培养期间，既能诱导抗体依赖性细胞毒性（ADCC），又能诱导肿瘤坏死因子α（TNF-α）的释放。尽管抗LeY单克隆抗体介导的TNF-α释放与ADCC活性平行，但细胞因子释放所需的致敏单克隆抗体浓度高于诱导细胞溶解所需的浓度。对参与诱导不同效应功能的FcgammaR类别进行测定表明，抗LeY单克隆抗体诱导的细胞溶解是由抗LeY单克隆抗体与FcgammaRI之间的相互作用触发的。相反，单克隆抗体诱导的TNF-α释放主要取决于单核细胞FcgammaRII的激活。TNF-α的中和对单核细胞对SKBR5靶细胞的ADCC活性没有影响。我们的数据表明，抗LeY单克隆抗体诱导的ADCC效应功能和TNF-α释放是独立调节的，这似乎是由不同类型的FcgammaR激活触发的。
