Sullivan G W, Carper H T, Mandell G L
Department of Medicine, University of Virginia, Charlottesville 22908.
Blood. 1993 Apr 1;81(7):1863-70.
Hematopoietic growth factors not only modulate blood progenitor cell activity but also alter the function of mature phagocytes. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 1 ng/mL for 60 min) did not stimulate luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMNs) in suspension but primed PMN for as much as a 15-fold increase in chemiluminescence in response to f-met-leu-phe (fMLP). Mixed mononuclear leukocytes (monocytes [approximately 20%] and lymphocytes [approximately 80%]; MNL) chemiluminescence was very low even after rhGM-CSF priming, but MNLs added to the PMNs (PMN-MNL) resulted in near doubling of rhGM-CSF-primed PMN fMLP-stimulated chemiluminescence. The enhancing factor(s) from MNLs were inherent rather than induced by the GM-CSF, and purified lymphocytes increased GM-CSF-primed PMN chemiluminescence equal to mixed MNLs. We could not detect cell-free "enhancing factor(s)," but cell-to-cell contact further enhanced rhGM-CSF-primed fMLP-stimulated PMN-MNL oxidative activity by 40%. Polyclonal rabbit anti-tumor necrosis factor (TNF) (but not preimmune serum) decreased both fMLP-stimulated rhGM-CSF-primed PMNs and PMN-MNL chemiluminescence, suggesting that TNF on the PMN surface is enhancing GM-CSF-primed chemiluminescence. GM-CSF priming markedly increased PMN superoxide release (sevenfold), but PMN superoxide release was not further enhanced by the presence of MNLs. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) and interleukin-3 (rhIL-3) displayed much smaller effects on pure PMNs and mixed PMN-MNL chemiluminescence and superoxide release than rhGM-CSF. rhGM-CSF primes PMNs for increased oxidative activity more than rhG-CSF and rhIL-3. Maximal oxidative activity was observed when mixed PMN-MNL were primed with GM-CSF in a cell pellet-promoting cell-to-cell contact. This enhanced activity can be attributed, in part, to both inherent enhancing factor(s) on lymphocytes and PMN-associated TNF induced by GM-CSF.
造血生长因子不仅能调节血液祖细胞的活性，还能改变成熟吞噬细胞的功能。重组人粒细胞 - 巨噬细胞集落刺激因子（rhGM - CSF；1 ng/mL，作用60分钟）不会刺激悬浮状态下多形核白细胞（PMN）的鲁米诺增强化学发光，但能使PMN对f - 甲硫 - 亮 - 苯丙氨酸（fMLP）产生的化学发光增强多达15倍。混合单核白细胞（单核细胞[约20%]和淋巴细胞[约80%]；MNL）即使在rhGM - CSF预处理后化学发光也很低，但将MNL加入PMN（PMN - MNL）中会使rhGM - CSF预处理的PMN对fMLP刺激的化学发光增加近一倍。来自MNL的增强因子是内在的，而非由GM - CSF诱导产生，纯化的淋巴细胞增强GM - CSF预处理的PMN化学发光的程度与混合MNL相同。我们无法检测到无细胞的“增强因子”，但细胞间接触使rhGM - CSF预处理的fMLP刺激的PMN - MNL氧化活性进一步增强了40%。多克隆兔抗肿瘤坏死因子（TNF）（而非免疫前血清）降低了fMLP刺激的rhGM - CSF预处理的PMN和PMN - MNL的化学发光，这表明PMN表面的TNF增强了GM - CSF预处理的化学发光。GM - CSF预处理显著增加了PMN超氧化物释放（7倍），但MNL的存在并未进一步增强PMN超氧化物释放。重组人粒细胞集落刺激因子（rhG - CSF）和白细胞介素 - 3（rhIL - 3）对纯PMN和混合PMN - MNL化学发光及超氧化物释放的影响比rhGM - CSF小得多。与rhG - CSF和rhIL - 3相比，rhGM - CSF使PMN的氧化活性增强作用更显著。当混合PMN - MNL在促进细胞间接触的细胞沉淀中用GM - CSF预处理时，观察到最大氧化活性。这种增强的活性部分可归因于淋巴细胞上的内在增强因子和GM - CSF诱导的PMN相关TNF。
