Zwahlen R D, Roth D R, Wyder-Walther M
Institute of Veterinary Pathology, University of Bern, Switzerland.
Inflammation. 1990 Aug;14(4):375-87. doi: 10.1007/BF00914089.
Deficient in vitro functions of neonatal neutrophils have been reported in various species. They may be functionally related to the well-known susceptibility of newborn individuals to microbial infections. To evaluate an early step in the sequence of neutrophil activation, neutrophils from adult cows (A-PMN) and newborn calves (N-PMN) were stimulated with zymosan-activated plasma (ZAP) or with the lipid mediator platelet-activating factor (PAF): Aggregation was recorded kinetically in a standard aggregometer and measured quantitatively as the area under the aggregation curve (AUAC). The mean +/- SEM of the AUAC of the first 2.5 min of the reaction induced with ZAP was similar in N-PMN and A-PMN. However, N-PMN deaggregated only partially, whereas A-PMN deaggregated almost completely (P less than 0.05). This may indicate a mechanism of microvascular sequestration in vivo with the potential to inhibit chemotaxis. PAF (10(-5)-10(-10) M) aggregated N- and A-PMNs similarly and dose-dependently with a maximal reaction at 10(-6) M. Inhibition of aggregation induced by 10(-6) M PAF was evaluated by preincubation with four antiinflammatory drugs: dexamethasone (Dex: 5.1, 51.0, 510.0 microM), flumethasone (Flu: 12.2 and 122.0 microM), phenylbutazone (PB: 0.33 and 3.3 mM), and flunixin meglumine (Flxin: 51 and 510 microM). Dex and Flu each inhibited (P less than 0.05) PAF-induced N-PMN aggregation at the highest dose, and A-PMN aggregation at the two higher doses. PB and Flxin each inhibited aggregation of N- and A-PMNs at all doses used. We compared the inhibition rate in both age groups and could demonstrate that Dex, Flu, and Flxin each at the highest dose, and PB at all doses used, inhibited PAF-induced aggregation less (P less than 0.05) in N-PMNs than in A-PMNs. These functional differences indicate hyperirritability of N-PMNs, and they need further elucidation to help understand mechanisms of increased neonatal susceptibility.
已有报道称,多种物种的新生中性粒细胞存在体外功能缺陷。它们可能在功能上与新生儿个体对微生物感染的众所周知的易感性有关。为了评估中性粒细胞激活序列中的早期步骤,用酵母聚糖激活血浆(ZAP)或脂质介质血小板激活因子(PAF)刺激成年母牛(A-PMN)和新生小牛(N-PMN)的中性粒细胞:在标准聚集仪中动态记录聚集情况,并将其定量测量为聚集曲线下的面积(AUAC)。ZAP诱导反应的前2.5分钟,N-PMN和A-PMN的AUAC的平均值±标准误相似。然而,N-PMN仅部分解聚,而A-PMN几乎完全解聚(P<0.05)。这可能表明体内微血管隔离的一种机制,具有抑制趋化作用的潜力。PAF(10^(-5)-10^(-10) M)以相似且剂量依赖性的方式聚集N-PMN和A-PMN,在10^(-6) M时反应最大。通过与四种抗炎药物预孵育来评估10^(-6) M PAF诱导的聚集抑制:地塞米松(Dex:5.1、51.0、510.0 microM)、氟米松(Flu:12.2和122.0 microM)、保泰松(PB:0.33和3.3 mM)和氟尼辛葡甲胺(Flxin:51和510 microM)。Dex和Flu在最高剂量时均抑制(P<0.05)PAF诱导的N-PMN聚集,在两个较高剂量时抑制A-PMN聚集。PB和Flxin在所有使用剂量下均抑制N-PMN和A-PMN的聚集。我们比较了两个年龄组的抑制率,结果表明,Dex、Flu和Flxin在最高剂量时,以及PB在所有使用剂量下,对PAF诱导的N-PMN聚集的抑制作用均小于A-PMN(P<0.05)。这些功能差异表明N-PMN具有高度易激性,需要进一步阐明以帮助理解新生儿易感性增加的机制。