Kenny P A, McDonald P J, Finlay-Jones J J
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
FEMS Immunol Med Microbiol. 1993 Oct;7(3):271-9. doi: 10.1111/j.1574-695X.1993.tb00408.x.
A range of recombinant cytokines have now been shown to modify aspects of the phenotype and function of human and murine neutrophils. However, few reports describe modification of the bactericidal activity of neutrophils. We therefore examined the recombinant murine cytokines tumor necrosis factor-alpha (TNF-alpha, 10-1000 ng ml-1) and granulocyte macrophage-colony stimulating factor (GM-CSF, 10-1000 U ml-1) for their ability to increase the bacterial killing capacity of murine neutrophils. Neutrophils from either bone marrow (fresh or cultured), or peritoneal exudates, or abscesses, were pre-incubated with either cytokine for 30-60 min and the killing of Proteus mirabilis, Escherichia coli, or Bacteroides fragilis was examined in the presence or absence of serum over a 90 min period. Only for one combination was a small but significantly enhanced level of bacterial killing observed, the phagocytic killing of P. mirabilis by peritoneal exudate neutrophils in the presence of GM-CSF and serum. With this exception there was no enhancement of bacterial killing for the range of combinations of neutrophils and bacterial species tested. In contrast, at the concentrations tested for effect on bactericidal activity, TNF-alpha and GM-CSF were able to significantly upregulate CR3 (but not Fc gamma RII) expression on mouse neutrophils. These results indicate that upregulation of CR3 as an index of neutrophil activation does not necessarily correlate with increased bactericidal activity.
现已表明,一系列重组细胞因子可改变人和小鼠中性粒细胞的表型及功能。然而,很少有报告描述对中性粒细胞杀菌活性的改变。因此,我们检测了重组小鼠细胞因子肿瘤坏死因子-α(TNF-α,10 - 1000 ng/ml)和粒细胞巨噬细胞集落刺激因子(GM-CSF,10 - 1000 U/ml)增强小鼠中性粒细胞细菌杀伤能力的能力。将来自骨髓(新鲜或培养的)、腹膜渗出液或脓肿的中性粒细胞与任一细胞因子预孵育30 - 60分钟,然后在有或无血清存在的情况下,在90分钟内检测奇异变形杆菌、大肠杆菌或脆弱拟杆菌的杀伤情况。仅有一种组合观察到细菌杀伤水平有小幅但显著的提高,即腹膜渗出液中性粒细胞在GM-CSF和血清存在的情况下对奇异变形杆菌的吞噬杀伤。除此之外,在所测试的中性粒细胞和细菌种类的各种组合中,细菌杀伤均未增强。相比之下,在测试对杀菌活性有影响的浓度下,TNF-α和GM-CSF能够显著上调小鼠中性粒细胞上CR3(而非FcγRII)的表达。这些结果表明,作为中性粒细胞活化指标的CR3上调不一定与杀菌活性增加相关。