Doré M, Slauson D O, Neilsen N R
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Am J Vet Res. 1991 Mar;52(3):375-80.
Newborn calves have a high susceptibility to bacterial infections, which may be related to the impaired neutrophil defense functions in newborns. The oxygen-dependent production of the free radical superoxide anion (O2-) represents an important part of the leukocyte respiratory burst central to neutrophil-directed defenses against bacterial infection. Because protein kinase C (PKC) activation is considered to be an important step in the signal transduction pathway for the O2- generating system, we compared O2- production by newborn and adult bovine neutrophils stimulated with 3 different PKC agonists. When the phorbol ester phorbol 12-myristate 13-acetate (PMA) was used, PKC-dependent O2- generation from newborn neutrophils was significantly reduced (P less than 0.01) for all concentrations of PMA tested (10, 100, and 500 ng/ml). In addition, newborn neutrophils had a significantly (P less than 0.01) reduced lag time for O2- generation. Similar significantly (P less than 0.01) reduced O2- generation from newborn neutrophils was observed with an additional phorbol ester (phorbol 12,13-dibutyrate); lag times were not calculated for phorbol 12,13-dibutyrate. When O2- generation was stimulated with a synthetic diacylglycerol analogue (1,2-dioctanoyl-sn-glycerol), less O2- was generated from both adult and newborn neutrophils than was obtained with the phorbol esters, and newborn neutrophils produced significantly (P less than 0.01) less O2- only at 50 microM 1,2-dioctanoyl-sn-glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)
新生小牛对细菌感染高度敏感,这可能与新生儿中性粒细胞防御功能受损有关。自由基超氧阴离子(O2-)的氧依赖性产生是白细胞呼吸爆发的重要组成部分,而白细胞呼吸爆发是中性粒细胞抵御细菌感染的核心防御机制。由于蛋白激酶C(PKC)激活被认为是O2-生成系统信号转导途径中的重要一步,我们比较了用3种不同PKC激动剂刺激的新生和成年牛中性粒细胞产生O2-的情况。当使用佛波酯佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)时,在所有测试浓度的PMA(10、100和500 ng/ml)下,新生中性粒细胞中PKC依赖性O2-的产生均显著减少(P<0.01)。此外,新生中性粒细胞产生O2-的延迟时间显著缩短(P<0.01)。使用另一种佛波酯(佛波醇12,13-二丁酸酯)时,也观察到新生中性粒细胞中O2-的产生显著减少(P<0.01);未计算佛波醇12,13-二丁酸酯的延迟时间。当用合成二酰基甘油类似物(1,2-二辛酰基-sn-甘油)刺激O2-产生时,成年和新生中性粒细胞产生的O2-均比用佛波酯时少,并且仅在50 microM 1,2-二辛酰基-sn-甘油时,新生中性粒细胞产生的O2-显著减少(P<0.01)。(摘要截断于250字)