Kitagawa S, Yuo A, Yagisawa M, Azuma E, Yoshida M, Furukawa Y, Takahashi M, Masuyama J, Takaku F
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Exp Hematol. 1996 Mar;24(4):559-67.
Tumor necrosis factor (TNF), like granulocyte-macrophage colony-stimul ating factor (GM-CSF), rapidly primed human monocytes for enhanced release of superoxide (O-2) stimulated by receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate (PMA), which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of suspended monocytes with 10 U/mL TNF for 10 minutes at 37 degrees C. The potency of the maximal priming effect was TNF> GM-CSF, and the combined effect of TNF and GM-CSF was greater than that of each cytokine alone. GM-CSF induced an increase in cytoplasmic pH but TNF did not. These findings suggest that TNF and GM-CSF activate monocytes through different mechanisms. TNF and GM-CSF by themselves never triggered O-2 release in suspended monocytes or monocytes adherent to endothelial cells, although both cytokines triggered massive release of O-2 in human neutrophils. In additions, TNF and GM-CSF induced tyrosine phosphorylation of a 42-kD protein in neutrophils but not in monocytes. These findings suggest that the TNF-receptor- or GM-CSF-receptor-mediated signaling pathways for triggering O-(2) release is active in neutrophils but inactive or defective in monocytes. TNF also enhanced phagocytosis of sialidase-treated autologous erythrocytes by monocytes, and this effect was further potentiated in the presence of autologous fresh serum. The significant enhancement of erythrophagocytosis was obtained at 1 U/mL TNF. At this concentration of TNF, the expression of C3bi-receptor (CD11b/CD18) was upregulated. These findings show that TNF rapidly primes human monocytes for enhanced release of O-(2) and erythrophagocytosis and suggest that TNF activates monocytes through autocrine or paracrine mechanisms at the inflammatory sites inasmuch as TNF is primarily produced by activated monocytes/macrophages.
肿瘤坏死因子（TNF）与粒细胞巨噬细胞集落刺激因子（GM-CSF）一样，能迅速使人类单核细胞致敏，从而增强受体介导的激动剂N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）和刀豆球蛋白A（Con A）刺激下的超氧化物（O₂⁻）释放，但不能增强佛波酯（PMA）刺激下的超氧化物释放，因为PMA绕过受体来刺激细胞。通过在37℃下用10 U/mL TNF预处理悬浮的单核细胞10分钟可获得最佳致敏效果。最大致敏效应的效力为TNF＞GM-CSF，且TNF和GM-CSF的联合效应大于每种细胞因子单独作用的效应。GM-CSF可诱导细胞质pH升高，但TNF则不能。这些发现表明TNF和GM-CSF通过不同机制激活单核细胞。TNF和GM-CSF本身从未在悬浮的单核细胞或黏附于内皮细胞的单核细胞中触发O₂⁻释放，尽管这两种细胞因子都能在人类中性粒细胞中触发大量O₂⁻释放。此外，TNF和GM-CSF可诱导中性粒细胞中一种42-kD蛋白的酪氨酸磷酸化，但不能诱导单核细胞中该蛋白的酪氨酸磷酸化。这些发现表明，TNF受体或GM-CSF受体介导的触发O₂⁻释放的信号通路在中性粒细胞中是活跃的，但在单核细胞中不活跃或有缺陷。TNF还增强了单核细胞对唾液酸酶处理的自体红细胞的吞噬作用，并且在存在自体新鲜血清的情况下这种效应进一步增强。在1 U/mL TNF时可显著增强红细胞吞噬作用。在此TNF浓度下，C3bi受体（CD11b/CD18）的表达上调。这些发现表明TNF能迅速使人类单核细胞致敏以增强O₂⁻释放和红细胞吞噬作用，并表明TNF在炎症部位通过自分泌或旁分泌机制激活单核细胞，因为TNF主要由活化的单核细胞/巨噬细胞产生。
