Boxer L A, Baehner R L, Davis J
J Cell Physiol. 1977 Apr;91(1):89-102. doi: 10.1002/jcp.1040910110.
The effects of 2-deoxyglucose (DOG), an inhibitor of glycolysis, on guinea pig polymorphonuclear leukocytes (PMN) obtained from peritoneal exudates was examined. ATP levels in PMN were reduced by 40% by one hour following an incubation with 2-deoxyglucose. When complement (C3) coated 14C-staphylococcus aureus, C3 coated lipopolysaccharide-paraffin oil droplets (LPS-PO), 14C-pneumococcus opsonized with IgG, or albumin coated paraffin oil droplets opsonized with IgG were added to cell suspensions containing DOG, the phagocytizing rate was 1,310+/-55 cpm/5 X 10(6) cells/15 minutes, 6+/-2 microng paraffin oil (PO)/10(7) cells/minute, 2,250+/-175 cpm/1 X 10(6) cells/20 minutes or 0.037+/-0.01 mg PO/10(7) cells/minute compared to control values of 5,970+/-275 cpm/5 X 10(6) cells/15 minutes, 35+/-3 microng PO/10(7) cells/15 minutes, 4,510+/-200 cpm/1 X 10(6) cells/20 minutes and 0.067+/-0.01 mg PO/10(7) cells/minute. In parallel studies the phagocytic index for latex was 0.74+/-0.28 in DOG compared to control of 2.36+/-1.13 and the phagocytic rate of albumin coated paraffin oil droplets was 0.029+/-0.01 mg PO/10(7) PMN/minute in DOG compared to control of 0.048 mg PO/10(7) cells/minute. When ATP levels were maintained by the simultaneous addition of 5 mM glucose or pyruvate to media containing DOG, latex ingestion was improved to 1.15+/-0.3 with glucose and 1.59+/-0.64 with pyruvate and albumin coated particles to 0.045+/-0.01 mg PO/10(7) PMN/minute with pyruvate. There was no improvement in the uptake of either the C3 dependent particles or IgG coated Pneumococci in media containing DOG and glucose and/or pyruvate. Following the removal of DOG from the extracellular medium and the addition of pyruvate or glucose, phagocytosis of C3 dependent LPS-PO was restored to normal values. Neither the binding of C3 or IgG coated particles to the PMN nor the lateral movement of glycoprotein utilizing concanavalin A capping was affected by DOG. Thus, the presence of DOG in the PMN containing adequate amounts of ATP will selectively and reversibly inhibit those surface events required for phagocytosis of C3 and IgG bound particles but not latex particles or albumin particles which non-specifically bind to PMN.
研究了糖酵解抑制剂2-脱氧葡萄糖(DOG)对从豚鼠腹腔渗出液中获取的多形核白细胞(PMN)的影响。用2-脱氧葡萄糖孵育1小时后,PMN中的ATP水平降低了40%。当将补体(C3)包被的14C-金黄色葡萄球菌、C3包被的脂多糖-石蜡油滴(LPS-PO)、用IgG调理的14C-肺炎球菌或用IgG调理的白蛋白包被的石蜡油滴加入含有DOG的细胞悬液中时,吞噬率分别为1,310±55 cpm/5×10(6)细胞/15分钟、6±2微克石蜡油(PO)/10(7)细胞/分钟、2,250±175 cpm/1×10(6)细胞/20分钟或0.037±0.01毫克PO/10(7)细胞/分钟,而对照值分别为5,970±275 cpm/5×10(6)细胞/15分钟、35±3微克PO/10(7)细胞/15分钟、4,510±200 cpm/1×10(6)细胞/20分钟和0.067±0.01毫克PO/10(7)细胞/分钟。在平行研究中,DOG组中乳胶的吞噬指数为0.74±0.28,而对照组为2.36±1.13;DOG组中白蛋白包被的石蜡油滴的吞噬率为0.029±0.01毫克PO/10(7)PMN/分钟,而对照组为0.048毫克PO/10(7)细胞/分钟。当在含有DOG的培养基中同时添加5 mM葡萄糖或丙酮酸以维持ATP水平时,葡萄糖使乳胶摄取改善至1.15±0.3,丙酮酸使其改善至1.59±0.64,丙酮酸使白蛋白包被颗粒的摄取改善至0.045±0.01毫克PO/10(7)PMN/分钟。在含有DOG和葡萄糖和/或丙酮酸的培养基中,C3依赖性颗粒或IgG包被的肺炎球菌的摄取没有改善。从细胞外培养基中去除DOG并添加丙酮酸或葡萄糖后,C3依赖性LPS-PO的吞噬恢复到正常水平。DOG既不影响C3或IgG包被颗粒与PMN的结合,也不影响利用伴刀豆球蛋白A封端的糖蛋白的侧向移动。因此,在含有足够量ATP的PMN中存在DOG将选择性地和可逆地抑制吞噬C3和IgG结合颗粒所需的那些表面事件,但不抑制非特异性结合PMN的乳胶颗粒或白蛋白颗粒。