A critical concentration of neutrophils is required for effective bacterial killing in suspension

A critical concentration of neutrophils is required for effective bacterial killing in suspension
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DOI:
10.1073/pnas.122244799
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发表时间:
2002-06-11
影响因子:
11.1
通讯作者:
Silverstein, SC
Silverstein, SC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li, YM;Karlin, A;Silverstein, SC

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我们研究了中性粒细胞浓度对表皮葡萄球菌临床分离株的杀伤作用。将浓度为10(5)~ 10(7)/ml的人中性粒细胞与浓度为103 ~ 108集落形成单位/ml的表皮葡萄球菌混合在悬浮液中,在37℃温度下测定不同时间后活菌的浓度。细菌的杀灭率取决于中性粒细胞的浓度,而不是中性粒细胞与细菌的比例。在中性粒细胞的临界浓度以下,即使中性粒细胞与细菌的比例为100:1,细菌的生长也大于中性粒细胞对细菌的杀伤。我们用指数函数拟合细菌浓度的时间过程及其对中性粒细胞浓度的依赖,指数为(-kp + g)t,其中k为细菌杀灭的二级速率常数,p为中性粒细胞浓度,g为细菌生长的一级速率常数,t为时间。我们发现k约为每中性粒细胞每分钟2 × 10(-8) ml, g约为8 × 10(-3)/min。只有当p大于g/k,也就是我们所说的中性粒细胞临界浓度时,细菌浓度才会下降。在最佳检测条件下,中性粒细胞临界浓度为3-4 × 10(5) / ml,这个值非常接近已知的使人类易受细菌和真菌感染的值(小于或等于5 × 10(5) / ml)。
We have examined the effect of neutrophil concentration on killing of a clinical isolate of Staphylococcus epidermidis. Human neutrophils at concentrations varying from 10(5) to 10(7) per ml were mixed in suspension with S. epidermidis at concentrations varying from 103 to 108 colony-forming units/ml, and the concentration of viable bacteria was assayed after various times at 37degreesC. The rate of bacterial killing depended on the concentration of neutrophils and not on the ratio of neutrophils to bacteria. Below a critical concentration of neutrophils, bacteria growth was greater than neutrophil killing of bacteria even when the ratio of neutrophils to bacteria was 100:1. We fitted the time course of bacterial concentration and its dependence on neutrophil concentration with an exponential function, the exponent of which is (-kp + g)t, where k is the second-order rate constant for bacterial killing, p is the neutrophil concentration, g is the first-order rate constant for bacterial growth, and t is time. We found that k approximate to 2 x 10(-8) ml per neutrophil per min, and g approximate to 8 x 10(-3)/min. Only when p is greater than g/k, which we call the critical neutrophil concentration, does the bacterial concentration fall. Under optimal assay conditions, the critical neutrophil concentration was 3-4 x 10(5) per ml, a value very close to that (less than or equal to5 x 10(5) per ml) known to predispose humans to bacterial and fungal infections.