Clinic of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
Clin Hemorheol Microcirc. 2012;51(4):293-301. doi: 10.3233/CH-2012-1536.
Activated polymorphonuclear neutrophils (PMN) play an important role in the microcirculation. Nitric oxide (NO) reduces the sequestration of PMN in the narrow vessels of various organs and, therefore, may reduce organ injury during inflammation.
Since PMN of term neonates show various functional differences compared to PMN in adults (decreased chemotaxis, decreased intracellular killing, decreased adhesion), we studied the influence of the semi-synthetical NO-donor FK-409 (4-Ethyl-2-hydroxyimino-5-nitro-3-hexenamide) on the deformability of IL-8 activated PMN in term neonates and adults.
A cell transit analyzer (CTA) was used to study transit times of individual PMN through 8 μm filter pores, neutrophil elastase concentrations were determined by enzyme-immunoessay and activation of PMN was classified by mircroscopic evaluation.
The transit times of PMN activated by IL-8 in adults were 9.3 ± 2.9 s, in term neonates 10.7 ± 3.3 s. FK-409 improved the transit time of activated PMN in adults (5.4 ± 1.6 s) and in term neonates (5.6 ± 1.1 s). Despite of the functional differences of PMN in term neonates and adults, the improvement of the transit times by FK-409 was not different between the two groups. The NO donor decreased the neutrophil elastase concentrations and the morphological signs of activation in neonates and adults.
We conclude that the NO-donor FK-409 improves the microcirculation by increasing the deformability of IL-8 activated PMN. NO may reduce in neonates tissue damage by reduced PMN sequestration due to decreased PMN rigidity.
活化的多形核粒细胞（PMN）在微循环中起着重要作用。一氧化氮（NO）可减少PMN在各种器官的狭窄血管中的扣押，从而可能减轻炎症期间的器官损伤。
由于足月新生儿的PMN与成人PMN相比具有各种功能差异（趋化性降低、细胞内杀伤降低、黏附降低），因此我们研究了半合成 NO 供体 FK-409（4-乙基-2-羟基亚氨基-5-硝基-3-己烯酰胺）对 IL-8 激活的足月新生儿和成人PMN变形能力的影响。
使用细胞传输分析仪（CTA）研究单个PMN 通过 8μm 滤孔的传输时间，通过酶免疫测定法测定中性粒细胞弹性蛋白酶浓度，并通过显微镜评估PMN 的激活情况。
IL-8 激活的PMN 在成人中的传输时间为 9.3±2.9s，在足月新生儿中为 10.7±3.3s。FK-409 改善了成人（5.4±1.6s）和足月新生儿（5.6±1.1s）中激活的PMN的传输时间。尽管足月新生儿和成人PMN 的功能存在差异，但 FK-409 对PMN 传输时间的改善在两组之间没有差异。NO 供体降低了新生儿和成人的中性粒细胞弹性蛋白酶浓度和形态激活迹象。
我们得出结论，NO 供体 FK-409 通过增加 IL-8 激活的PMN 的变形能力来改善微循环。由于PMN 刚性降低，NO 可能通过减少PMN 扣押来减少新生儿组织损伤。
