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Neutrophil Receptor Response to Bacterial N-formyl Peptides is Similar in Term Newborn Infants and Adults in Contrast to IL-8
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)
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)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2016 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 84, no 6, p. 332-337Article in journal (Refereed) Published
Abstract [en]

We have previously observed that neutrophils from neonates exhibit different migratory responses to intermediate and end-target chemoattractants compared to adults. The aim of the present study was to investigate the effect of the chemoattractants IL-8 (intermediate) and formyl-methionine-leucyl-phenylalanine (fMLP; end-target) on cell surface receptor expression involved in adhesion, migration and granule release of neutrophils from term newborn infants and adults. Heparinized cord blood from 16 healthy term infants delivered by caesarean section and peripheral blood from 17 healthy adults were incubated with 1 μM IL-8 or 0.01 μM fMLP, previously defined as optimal inducers of neutrophil migration. The leukocytes were labelled with antibodies to cell surface receptors (CD11b, CD15S, CD18, CD35, CD44, CD64, CD65, CD88, CD162, CD181 and CD182). Receptor expression was quantified by flow cytometry analysis. Up regulation of CD11b and down regulation of CD88 and CD182 after stimulation with IL-8, was more pronounced in adults than in neonates (p<0.05, p<0.05 and p≤0.001 respectively), whereas fMLP induced changes in receptor expression that were of the same magnitude in neutrophils from neonates as from adults. We observed similar expression of receptors that mediate adhesion, migration, granule activation, and phagocytosis induced by fMLP in neutrophils from neonates and adults. In contrast, differences between neonates and adults, induced by IL-8, suggest that the neutrophil response to intermediate chemoattractants might lead to a compromised infectious response in newborn infants.

Place, publisher, year, edition, pages
2016. Vol. 84, no 6, p. 332-337
Keywords [en]
neutrophils, cell surface molecules, term newborn infants, IL-8, fMLP
National Category
Immunology in the medical area
Research subject
Immunology; Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-304757DOI: 10.1111/sji.12477ISI: 000393285400005PubMedID: 27606963OAI: oai:DiVA.org:uu-304757DiVA, id: diva2:1033912
Available from: 2016-10-10 Created: 2016-10-10 Last updated: 2018-01-14Bibliographically 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. p. 47
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1265
Keywords
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, MariaSindelar, RichardDouhan Håkansson, Lena

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