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Compromised Ability to Modulate Neutrophil Respiratory Burst in Very Pretem Newborn Infants -A Pilot Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Perinatal, neonatal och barnkardiologisk forskning/Westas)
2016 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Chemotaxis and respiratory burst can be compromised in preterm newborn infants where sustained neutrophil accumulation, reduced scavenging, and uncontrolled burst might cause inadvertent tissue damage. Neutrophil respiratory burst induced by phorbol myristate acetate (PMA) and E.coli can be reduced by the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP), but not IL-8, in full term newborn infants and adults. The aim of this study was to investigate whether a similar modulatory response on respiratory burst could be detected in neutrophils from very preterm newborn infants.

Methods: Whole blood from eight preterm infants (median 25+3weeks GA; range 23+0–29+2) was collected within three days of birth (median 1.4 days PNA; range 0.4 – 2.5 days) and preincubated with fMLP or IL-8 prior to stimulation with PMA or E.coli bacteria. Respiratory burst was registered by flow cytometry analysis of rhodamine fluorescence.

Results: All infants responded with an increased neutrophil respiratory burst to PMA and E.coli, but with a higher response to PMA than to E.coli (p<0.05). Although no significant modulation of neutrophil respiratory burst by preincubation with fMLP or IL-8 was observed in the whole group, there was a reduced PMA-induced burst with fMLP (p=0.09), and more specifically in infants born >25 GA (n=4/4) than in <25 GA (n=2/4). Two extremely preterm neonates had a neutrophil sub population with a marked reduction in ROS production than with fMLP induced by PMA.

Conclusions: The fMLP reduction in PMA- and E.coli-induced respiratory burst of neutrophils in full term newborn infants and adults could not be confirmed in this pilot study of preterm infants. Although respiratory reduction was observed in more mature infants with fMLP, a compromised neutrophil respiratory burst modulation in very preterm infants could not be excluded: this requires further studies at different gestational and postnatal ages.

Place, publisher, year, edition, pages
2016.
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-305008OAI: oai:DiVA.org:uu-305008DiVA: diva2:1034348
Available from: 2016-10-11 Created: 2016-10-11 Last updated: 2016-10-13
In thesis
1. Neutrophil Chemotaxis and Respiratory Burst in Term and Preterm Newborn Infants
Open this publication in new window or tab >>Neutrophil Chemotaxis and Respiratory Burst in Term and Preterm Newborn Infants
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neutrophil activation is the most important initial immune defense against invading microbes in newborn infants. The reduced neutrophil migration and uncontrolled regulation of reactive oxygen species (ROS) production observed in neonates, could result in a diminished infectious response or in tissue damage. The aims were to study neutrophil chemotactic response towards IL-8 and fMLP in term neonates; to examine neutrophil receptor expression involved in adhesion, migration, phagocytosis and complement after stimulation with IL-8 and fMLP in term neonates; and to investigate neutrophil production of ROS, induced by PMA and E.coli, after preincubation with IL-8 and fMLP in term and preterm newborn infants. Comparisons were made to neutrophils from healthy adults.

Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil migration distance and the number of migrating neutrophils per distance was evaluated. Neutrophils were labeled with antibodies to cell surface antigens (CD11b, CD18, CD65, CD15S, CD162, CD44, CD35, CD88, CD181, CD182 and CD64) after stimulation with IL-8 and fMLP. After preincubation of neutrophils with fMLP or IL-8 and stimulation with PMA or E.coli, respiratory burst was detected. The same analyses were also made in preterm infants (median 25+3weeks GA; range 23+0–29+2) within 3 days postnatal age.

Neutrophils from neonates exhibited different migratory and receptor responses to IL-8 and fMLP, with a diminished response towards IL-8 in term newborn infants in terms of reduced chemotaxis and modulation of receptors involved in adhesion, chemotaxis, complement and phagocytosis as compared to adults. fMLP reduced PMA- and E.coli-induced respiratory burst in neutrophils from term neonates and adults. The reduced respiratory burst by fMLP may be a mechanism for reducing the detrimental effects of uncontrolled inflammation. Although a similar burst reduction was observed in preterm infants born >25 weeks GA with fMLP, a diminished neutrophil respiratory burst modulation in very preterm infants cannot be excluded and requires further studies at different gestational and postnatal ages.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1265
Keyword
innate immunity, neutrophil, term newborn infants, preterm newborn infants, chemotaxis, respiratory burst, reactive oxygen species, cell surface receptor, IL-8, bacterial N-formyl peptide
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-305009 (URN)978-91-554-9722-4 (ISBN)
Public defence
2016-11-23, C8:305, BMC, Husargatan 3, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-11-02 Created: 2016-10-11 Last updated: 2016-11-16

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