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The NO-donor FK409 improves mechanical properties of activated neonatal PMN
P Ruef1, E Craciun, D Frommhold
1Clinic of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany. peter.ruef@tonline.de
Background:
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.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Nitric oxide (NO) donor FK-409 enhances polymorphonuclear neutrophil (PMN) deformability in both neonates and adults. This improved PMN function may reduce tissue injury during inflammation by decreasing PMN sequestration in microcirculation.
Area of Science:
- Physiology
- Pharmacology
- Neonatal Medicine
Background:
- Activated polymorphonuclear neutrophils (PMN) are crucial in microcirculation.
- Nitric oxide (NO) can mitigate PMN sequestration and subsequent organ injury during inflammation.
Purpose of the Study:
- To investigate the effect of the NO-donor FK-409 on the deformability of IL-8 activated PMN in term neonates and adults.
- To compare the functional differences of PMN in neonates versus adults and FK-409's impact.
Main Methods:
- Utilized a cell transit analyzer (CTA) to measure PMN transit times through 8 μm filter pores.
- Quantified neutrophil elastase concentrations via enzyme-immunoessay.
- Assessed PMN activation through microscopic evaluation.
Main Results:
- FK-409 significantly improved PMN transit times in both adults and neonates, indicating enhanced deformability.
- The beneficial effect of FK-409 on PMN transit times was consistent across both age groups.
- FK-409 reduced neutrophil elastase levels and morphological signs of activation.
Conclusions:
- The NO-donor FK-409 enhances PMN deformability, thereby improving microcirculation.
- NO administration may reduce tissue damage in neonates by decreasing PMN rigidity and sequestration.
