Dallegri F, Ottonello L, Ballestrero A, Dapino P, Ferrando F, Patrone F, Sacchetti C
First Medical Clinic, University of Genova Medical School, Italy.
Inflammation. 1991 Feb;15(1):15-30. doi: 10.1007/BF00917906.
The lysis of tumor cells, and other nucleated mammalian cells, by neutrophilic polymorphonuclear leukocytes (PMNs) triggered by phorbol myristate acetate (PMA) represents a widely used model system to dissect the PMN cytolytic armamentarium, potentially responsible for the cell damage at tissue sites of PMN activation. Although oxidants are generally considered to be instrumental in the target lysis by PMNs, the mediators actually involved remain a matter of controversy. Moreover, other factors potentially crucial to the lysis have not been clearly identified. In order to reexamine the determinants of the cytolytic process, we studied the events underlying the PMA-triggered PMN-delivered attack against two different targets, selected on the basis of preliminary experiments (B lymphoblastoid Daudi cells and erythroleukemic K 562 cells). The results suggest that the lysis is promoted by hypochlorous acid (HOCl) or a compound with characteristics very similar to HOCl itself. No evidence was obtained for the intervention or contribution of hydrogen peroxide (H2O2), hydroxyl (OH.) radicals, and the major HOCl-derived chloramines. PMNs appeared to use 35% of the generated H2O2 to produce HOCl, while the remainder appears to be consumed by PMNs themselves and target cells as well. Moreover, PMNs and target cells coaggregated at an early step of the cytolytic reaction, through a process efficiently prevented by a monoclonal antibody (MoAb J-90) directed against leukocyte function-associated antigen-1 (LFA-1). The inhibition of the PMN-target aggregation by the MoAb J-90 resulted in the impairment of the lysis, despite a normal generation of HOCl. Thus, the data demonstrate that the PMA-triggered lysis of tumor target cells by PMNs requires at least two events, occurring simultaneously: the LFA-1-mediated effector-target adherence and the PMN production of HOCl. The intervention of the LFA-1-mediated PMN-target adherence in the PMA-triggered lysis is likely to allow PMNs to focus HOCl on the target cell surface and suggests that the process requires a sort of molecule to molecule recognition at the effector-target surface level.
佛波醇肉豆蔻酸酯乙酸酯（PMA）触发的嗜中性多形核白细胞（PMN）对肿瘤细胞及其他有核哺乳动物细胞的裂解，是一种广泛应用的模型系统，用于剖析PMN的溶细胞武器库，这可能是PMN激活组织部位细胞损伤的原因。尽管氧化剂通常被认为在PMN介导的靶细胞裂解中起作用，但实际涉及的介质仍存在争议。此外，其他对裂解可能至关重要的因素尚未明确。为了重新审视溶细胞过程的决定因素，我们研究了PMA触发的PMN对两种不同靶细胞发动攻击的潜在机制，这两种靶细胞是根据初步实验选定的（B淋巴母细胞样Daudi细胞和红白血病K 562细胞）。结果表明，裂解是由次氯酸（HOCl）或与HOCl本身特性非常相似的化合物促进的。未获得过氧化氢（H2O2）、羟基（OH·）自由基和主要的HOCl衍生氯胺参与或起作用的证据。PMN似乎利用35%生成的H2O2来产生HOCl，而其余部分似乎被PMN自身以及靶细胞消耗。此外，在溶细胞反应的早期阶段，PMN与靶细胞会发生共聚集，而针对白细胞功能相关抗原-1（LFA-1）的单克隆抗体（MoAb J-90）可有效阻止这一过程。尽管HOCl生成正常，但MoAb J-90对PMN-靶细胞聚集的抑制导致了裂解受损。因此，数据表明PMA触发的PMN对肿瘤靶细胞的裂解至少需要两个同时发生的事件：LFA-1介导的效应细胞-靶细胞黏附以及PMN产生HOCl。LFA-1介导的PMN-靶细胞黏附在PMA触发的裂解中的作用，可能是使PMN将HOCl聚焦于靶细胞表面，这表明该过程在效应细胞-靶细胞表面水平需要某种分子间的识别。
