Huang Ji-Biao, Kindzelskii Andrei L, Petty Howard R
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.
Cell Immunol. 2002 Jul-Aug;218(1-2):95-106. doi: 10.1016/s0008-8749(02)00582-8.
Neutrophils expend large amounts of energy to perform demanding cell functions. To better understand energy production and flow during cell activation, immunofluorescence microscopy was employed to determine the location of the key metabolic enzyme hexokinase during various conditions. Hexokinase is translocated from the neutrophil's cytosol to its periphery in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) and other activating stimuli, but not during exposure to the formyl peptide receptor antagonist N-tert-BOC-phe-leu-phe-leu-phe (Boc-PLPLP). Translocation was observed from 10(-6) to 10(-9)M fMLP. However, fMLP did not affect the intracellular distribution of lactate dehydrogenase. Hexokinase accumulated at the lamellipodium of cells exposured to an fMLP gradient whereas it localized to the phagosome after latex bead uptake. Thus, hexokinase is differentially translocated within cells depending upon the prevailing physiological conditions. Further studies noted that cytochalasin D, dexamethasone, and indomethacin blocked hexokinase translocation. Parallel regulation of reactive oxygen metabolite (ROM) production was shown. We speculate that hexokinase translocation participates in neutrophil activation.
中性粒细胞消耗大量能量来执行高要求的细胞功能。为了更好地理解细胞激活过程中的能量产生和流动，采用免疫荧光显微镜来确定关键代谢酶己糖激酶在各种条件下的位置。己糖激酶会响应N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）和其他激活刺激，从中性粒细胞的胞质溶胶转移至其外周，但在暴露于甲酰肽受体拮抗剂N-叔丁氧羰基-苯丙氨酰-亮氨酰-苯丙氨酰-亮氨酰-苯丙氨酸（Boc-PLPLP）时不会发生转移。在10⁻⁶至10⁻⁹M的fMLP浓度下观察到了转移现象。然而，fMLP并不影响乳酸脱氢酶的细胞内分布。己糖激酶在暴露于fMLP梯度的细胞的片状伪足处积聚，而在摄取乳胶珠后则定位于吞噬体。因此，己糖激酶在细胞内的转移因当时的生理条件而异。进一步的研究指出，细胞松弛素D、地塞米松和吲哚美辛会阻断己糖激酶的转移。同时还显示了活性氧代谢产物（ROM）产生的平行调节。我们推测己糖激酶的转移参与了中性粒细胞的激活。
