PHAGOCYTE-DERIVED LACTATE STIMULATES OXYGEN-CONSUMPTION BY NEISSERIA-GONORRHOEAE - AN UNRECOGNIZED ASPECT OF THE OXYGEN-METABOLISM OF PHAGOCYTOSIS
PHAGOCYTE-DERIVED LACTATE STIMULATES OXYGEN-CONSUMPTION BY NEISSERIA-GONORRHOEAE - AN UNRECOGNIZED ASPECT OF THE OXYGEN-METABOLISM OF PHAGOCYTOSIS
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DOI：
10.1172/jci113323
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发表时间：
1988-02-01
影响因子：
15.9
通讯作者：
COHEN, MS
中科院分区：
文献类型：
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作者：
BRITIGAN, BE;KLAPPER, D;COHEN, MS
淋病奈瑟菌和人嗜中性粒细胞相互作用导致的O2消耗代表两种细胞系统消耗的O2的复合物。研究每个系统的相对贡献的实验表明，淋球菌在与中性粒细胞相互作用时可能会增加其代谢活性。这一假设得到证实，表明未分化的HL-60细胞，这是无法进行呼吸爆发，诱导淋球菌O2消耗增加2至3倍。淋球菌粘附HL-60细胞的能力与代谢刺激的程度无关。刺激活性在中性粒细胞或HL-60细胞的无细胞上清液中可证实，并随孵育时间增加。上清液施加到G-15葡聚糖凝胶柱产生刺激淋球菌O2消耗的馏分。HL-60细胞、中性粒细胞和先前从合并人血清中分离的刺激因子的洗脱曲线相似。这种刺激因子不能粘附在DEAE或C-18 HPLC柱上。通过在4.0 ℃温育抑制髓样细胞的刺激活性释放。C或在NaF存在下，表明葡萄糖代谢的关键作用。乳酸盐是静息中性粒细胞葡萄糖催化剂的主要产物，在37 ℃温育后，在无细胞上清液中可证实。C. NaF和降低培养温度可抑制乳酸的积累。乳酸在无细胞上清液中的水平增加淋球菌O2消耗量的两倍，并恢复刺激活性透析血清。活淋球菌（而不是热灭活淋球菌）在吞噬过程中消除中性粒细胞释放的乳酸。淋球菌能够利用宿主来源的乳酸盐来提高其O2代谢速率。
O2 consumption resulting from interaction of Neisseria gonorrhoeae and human neutrophils represents a composite of O2 consumed by the two cell systems. Experiments studying the relative contribution of each system suggested the possibility that gonococci increased their metabolic activity in response to interaction with neutrophils. This hypothesis was confirmed by demonstrating that undifferentiated HL-60 cells, which are unable to undergo a respiratory burst, induce a two- to threefold increase in gonococcal O2 consumption. Gonococcal capacity to adhere to HL-60 cells did not correlate with extent of metabolic stimulation. Stimulatory activity was demonstrable in cell-free supernatant from neutrophils or HL-60 cells, and increased with duration of incubation. Supernatant applied to a G-15 Sephadex column yielded fractions that stimulated gonococcal O2 consumption. Elution profiles were similar for HL-60 cells, neutrophils, and a stimulatory factor previously isolated from pooled human serum. This stimulatory factor(s) failed to adhere to DEAE or C-18 HPLC columns. Stimulatory activity release from myeloid cells was inhibited by incubation at 4.degree. C or in the presence of NaF, indicating a critical role for glucose metabolism. Lactate, the principal product of resting neutrophil glucose catabolism, was demonstrable in cell-free supernatants after incubation at 37.degree. C. Lactate accumulation was inhibited by NaF and decreased temperature of incubation. Lactate at levels present in cell-free supernatant increased gonococcal O2 consumption twofold and restored stimulatory activity to dialyzed serum. Live, but not heat-killed gonococci eliminated lactate released from neutrophils during phagocytosis. Gonococci are able to utilize host-derived lactate to enhance their rate of O2 metabolism.