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Differential Neutrophil Chemotactic Response towards IL-8 and Bacterial N-formyl Peptides in Term Newborn Infants
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)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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)
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: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, 35-42 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A prerequisite for an effective innate immunity is the migrative ability of neutrophils to respond to inflammatory and infectious agents such as the intermediate interleukin (IL)-8 and the end-target formyl-methionyl-leucyl-phenylalanine (fMLP) chemoattractants. The aim was to study the chemotactic capacity of neutrophils from newborn infants and adults in response to IL-8 and the bacterial peptide fMLP.

METHODS: In the under-agarose cell migration assay, isolated leukocytes from healthy adults and from cord blood of healthy term newborn infants were studied with dose responses towards IL-8 and fMLP. The same number of leukocytes (1 × 10(5) cells), with the same distribution of neutrophils and monocytes, were analyzed in neonates and adults. Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil pattern of migration, i.e. the migration distance and the number of migrating neutrophils per distance, was evaluated.

RESULTS: In comparison to adults, fewer neutrophils from newborn infants migrated towards IL-8 and for a shorter distance (P < .01, respectively). The number of neutrophils migrating to different gradients of fMLP, the distance they migrated, and the correlation between the number and the distance were the same for neonates and adults. Random migration did not differ in any instance.

CONCLUSION: Chemotaxis of neutrophils from newborn infants was as co-ordinated as neutrophils from adults in response to fMLP, whereas the response to IL-8 was reduced. The differential response of neutrophils from neonates to intermediate and end-target chemoattractants could indicate a reduced infectious response.

Place, publisher, year, edition, pages
2017. Vol. 122, no 1, 35-42 p.
Keyword [en]
Chemotaxis, chemoattractants, fMLP, innate immunity, IL-8, neutrophils, newborn infants
National Category
Pediatrics Immunology in the medical area
Research subject
Immunology; Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-304756DOI: 10.1080/03009734.2016.1228721ISI: 000396476600005PubMedID: 27690722OAI: oai:DiVA.org:uu-304756DiVA: diva2:1033905
Available from: 2016-10-10 Created: 2016-10-10 Last updated: 2017-11-30Bibliographically 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, MariaHåkansson, Lena DouhanJonzon, AndersSindelar, Richard

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