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Bacterial N-formyl Peptides Reduce PMA and Escherichia coli-Induced Neutrophil Respiratory Burst in Term Neonates and Adults
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Perinatal, neonatal och barnkardiologisk forskning/Hellström-Westas)ORCID iD: 000-0003-1362-1714
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. (Perinatal, neonatal och barnkardiologisk forskning/Hellström-Westas)
2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 85, no 5, 365-371 p.Article in journal (Refereed) Published
Abstract [en]

Neutrophil migration and respiratory burst is the prerequisite for efficient first line defense against invading microorganisms. However, migration and respiratory burst can be compromised in adults and especially in newborn infants, where sustained neutrophil accumulation, uncontrolled burst and reduced scavenging of ROS might cause inadvertent tissue damage due to uncontrolled inflammation. The aim of this study was to investigate the modulatory effect of the chemoattractants formyl-methionyl-leucyl-phenylalanine (fMLP) and IL-8 on respiratory burst in neutrophils from term newborn infants and adults. Whole blood from the umbilical cord of 17 healthy term newborn infants delivered by caesarean section and from 17 healthy adults as reference was preincubated with fMLP or IL-8 and stimulated with PMA or E.coli bacteria. Respiratory burst was quantified by flow cytometry analysis of dihydrorhodamine 123 fluorescence. fMLP reduced the PMA-induced respiratory burst of neutrophils from newborn infants and adults by 12% and 21% respectively (p<0.05). E.coli-induced burst was also reduced by fMLP in neutrophils from newborn infants (10%; p<0.01) and adults (6%; p<0.05). No such changes were observed with IL-8. Similar respiratory burst in response to single stimulus with PMA or E.coli were observed in both newborn infants and adults. fMLP reduced PMA- and E.coli-induced respiratory burst of neutrophils in whole blood from term newborn infants as well as in adults. The reduced respiratory burst by fMLP might be a mechanism to reduce the detrimental effects of uncontrolled inflammation during neutrophil migration

Place, publisher, year, edition, pages
2017. Vol. 85, no 5, 365-371 p.
National Category
Immunology in the medical area
Research subject
Immunology; Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-214732DOI: 10.1111/sji.12537ISI: 000400011500006PubMedID: 28199745OAI: oai:DiVA.org:uu-214732DiVA: diva2:685476
Note

Title in Dissertation reference list: Bacterial N-formyl Peptides Reduce PMA and E.coli Induced Neutrophil Respiratory Burst in Term Neonates and Adults.

Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2017-06-01Bibliographically approved
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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Stålhammar, Maria E.Douhan Håkansson, LenaSindelar, Richard

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