Stiehm E R, Roberts R L, Ank B J, Plaeger-Marshall S, Salman N, Shen L, Fanger M W
Department of Pediatrics, UCLA School of Medicine, Los Angeles, California 90024-1752, USA.
Clin Diagn Lab Immunol. 1994 May;1(3):342-7. doi: 10.1128/cdli.1.3.342-347.1994.
We studied cytotoxic capabilities of newborn polymorphonuclear leukocytes (PMNs) and monocytes and their enhancement by cytokines and antibodies. Umbilical cord PMNs were assessed for their ability to kill various target cells spontaneously, after activation with phorbol myristate acetate, in the presence of antiserum (antibody-dependent cellular cytotoxicity), and in the presence of dually specific antibody (heteroantibody-mediated cytotoxicity). Target cells included the K562 cell line (natural killer cell target), chicken erythrocytes (CRBCs), and herpes simplex virus-infected CEM cell lines. Newborn PMNs were equivalent to adult PMNs in their cytotoxic capacity in several cytotoxicity assays. Neither adult nor newborn PMNs lyse tumor cell targets (i.e., K562 cells) spontaneously, but both lyse K562 cells following activation with phorbol myristate acetate. Both adult and newborn PMNs lyse CRBCs and herpes simplex virus-infected CEM cells in antibody-dependent cellular cytotoxicity assays, and this lysis could be enhanced by the cytokines granulocyte-macrophage colony-stimulating factor and gamma interferon. PMN heteroantibody-mediated cytotoxicity, resulting from the use of an antibody with dual specificity to CRBCs and immunoglobulin G FcRII, was greater in newborn PMNs than in adult PMNs; however, monocyte heteroantibody-mediated cytotoxicity, resulting from the use of an antibody to CRBCs and monocyte immunoglobulin G FcRI, was lower in newborn monocytes than in adult monocytes. The percentage, but not the density, of PMNs expressing FcRII was significantly reduced in newborn PMNs compared with that in adult PMNs, while the percentages and densities of FcRI expression were equivalent in newborn and adult monocytes. We conclude that the cytotoxic capability in term newborn PMNs is equivalent to that in adult PMNs, that the activity of newborn PMNs can be enhanced by antibody and/or cytokines, and that PMNs can contribute to the newborn's ability to kill virus-infected cells.
我们研究了新生儿多形核白细胞(PMN)和单核细胞的细胞毒性能力,以及细胞因子和抗体对其的增强作用。评估了脐带血PMN在自发状态下、用佛波酯肉豆蔻酸酯激活后、在抗血清存在下(抗体依赖性细胞毒性)以及在双特异性抗体存在下(异源抗体介导的细胞毒性)杀死各种靶细胞的能力。靶细胞包括K562细胞系(自然杀伤细胞靶标)、鸡红细胞(CRBC)和单纯疱疹病毒感染的CEM细胞系。在几种细胞毒性试验中,新生儿PMN的细胞毒性能力与成人PMN相当。成人和新生儿PMN均不会自发裂解肿瘤细胞靶标(即K562细胞),但在用佛波酯肉豆蔻酸酯激活后均可裂解K562细胞。在抗体依赖性细胞毒性试验中,成人和新生儿PMN均可裂解CRBC和单纯疱疹病毒感染的CEM细胞,细胞因子粒细胞-巨噬细胞集落刺激因子和γ干扰素可增强这种裂解作用。由于使用了对CRBC和免疫球蛋白G FcRII具有双特异性的抗体而导致的PMN异源抗体介导的细胞毒性,在新生儿PMN中比在成人PMN中更强;然而,由于使用了针对CRBC和单核细胞免疫球蛋白G FcRI的抗体而导致的单核细胞异源抗体介导的细胞毒性,在新生儿单核细胞中比在成人单核细胞中更低。与成人PMN相比,新生儿PMN中表达FcRII的PMN百分比显著降低,但密度无显著差异,而新生儿和成人单核细胞中FcRI表达的百分比和密度相当。我们得出结论,足月新生儿PMN的细胞毒性能力与成人PMN相当,新生儿PMN的活性可通过抗体和/或细胞因子增强,并且PMN可有助于新生儿杀死病毒感染细胞的能力。