Bactericidal capacity of phorbol myristate acetate-treated human polymorphonuclear leukocytes

Bactericidal capacity of phorbol myristate acetate-treated human polymorphonuclear leukocytes
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佛波醇肉豆蔻酸酯醋酸酯处理的人多形核白细胞的杀菌能力

DOI:
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发表时间:
1978
影响因子:
3.1
通讯作者:
M. Cooney
M. Cooney
中科院分区:
医学2区
文献类型:
--
作者:
P. Wang;K. Pryzwansky;J. Spitznagel;M. Cooney

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到目前为止,佛波醇肉豆蔻酸酯乙酸酯(PMA)处理的人多形核白细胞的功能能力尚未确定。PMA诱导乳铁蛋白(特异性颗粒标记物)的胞吐,但不诱导髓过氧化物酶(嗜天青颗粒标记物)的胞吐。这一现象在生物化学和荧光抗体偶联物中都得到了证实。PMA处理的中性粒细胞几乎没有特定的颗粒时,通过电子显微镜观察。通过线性蔗糖密度梯度离心分离颗粒类别揭示了从PMA处理的嗜中性粒细胞中损失乳铁蛋白和通常从正常嗜中性粒细胞中解析的特定颗粒(D20(20)= 1.89)带。用PMA处理的细胞似乎保留了通常与白细胞内杀微生物作用相关的那些功能。在PMA处理的中性粒细胞中存在吞噬细胞激发激活的单磷酸己糖分流。如电子显微镜所示,这些细胞的嗜天青颗粒似乎是完整的,它们保留了脱颗粒的能力,髓过氧化物酶易位到被吞噬的大肠杆菌的网站。PMA处理的中性粒细胞也仍然能够降解摄入的微生物。PMA处理的中性粒细胞在所有水平的细菌挑战中表现出吞噬能力降低。在存在大量细菌的情况下,它们表现出杀伤能力受损。这些相同的细胞能够杀死低倍数的E。coli以及对照细胞。因此,似乎特定颗粒的丢失,加上其他未定义的PMA诱导的改变,既不损害这些中性粒细胞的活力,也不损害它们在适度吞噬挑战存在下的杀伤能力。
Thus far, the functional capacity of phorbol myristate acetate- (PMA)-treated human polymorphonuclear leukocytes has been undefined. PMA induced exocytosis of lactoferrin, the specific granule marker, but not of myeloperoxidase, the azurophil granule marker. This phenomenon was demonstrated both biochemically and with fluorescent antibody conjugates. PMA-treated neutrophils contained virtually no specific granules when viewed by electron microscopy. Separation of the granule classes by linear sucrose density gradient centrifugation revealed the loss, from PMA-treated neutrophils, of lactoferrin and the specific granule (D20(20) = 1.89) band usually resolved from normal neutrophils. Cells treated with PMA appeared to retain those functions normally associated with intraleukocytic microbicidal action. The hexose monophosphate shunt activated by phagocytic challenge was present in PMA-treated neutrophils. As demonstrated by electron microscopy, the azurophil granules of these cells appeared intact, and they retained the capacity for degranulation with translocation of myeloperoxidase to the site of phagocytized Escherichia coli. The PMA-treated neutrophils also remained capable of degrading the ingested microorganisms. PMA-treated neutrophils exhibited a decrease in phagocytic ability at all levels of bacterial challenge. In the presence of a high multiplicity of bacteria they demonstrated an impairment in killing. These same cells were able to kill low multiplicities of E. coli as well as control cells. It thus appeared that the loss of the specific granules, plus other undefined PMA-induced alterations, impaired neither the viability of these neutrophils nor their killing ability in the presence of a modest phagocytic challenge.