Differential neutrophil chemotactic response towards IL-8 and bacterial N-formyl peptides in term newborn infants.
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 × 105cells), 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.


CONCLUSIONS
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.
a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
Maria E
ME
Stålhammar
b Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
Lena
L
Douhan Håkansson
a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
Anders
A
Jonzon
a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
Richard
R
Sindelar
D000293:Adolescent; D000328:Adult; D000368:Aged; D002465:Cell Movement; D002630:Chemotactic Factors / Q000737:chemistry; D002633:Chemotaxis; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000737:chemistry*; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000737:chemistry*; D009504:Neutrophils / Q000166:cytology*; D012685:Sepharose / Q000737:chemistry; D055815:Young Adult
C508606:CXCL8 protein, human; D002630:Chemotactic Factors; D016209:Interleukin-8; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012685:Sepharose
Chemotaxis; IL-8; chemoattractants; fMLP; innate immunity; neutrophils; newborn infants
J Clin Invest. 1981 Oct;68(4):863-74
7287906
J Biol Chem. 1998 Sep 11;273(37):23830-6
9726994
Pediatr Res. 1977 May;11(5):677-80
870874
Rev Physiol Biochem Pharmacol. 1991;117:1-338
1659735
Acta Paediatr Scand. 1990 Nov;79(11):1031-8
2267919
Eur J Immunol. 1997 Oct;27(10):2571-8
9368612
J Immunol Methods. 2008 Feb 29;331(1-2):50-8
18166194
AIDS. 1994 Jun;8(6):771-7
8086135
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6682-6
8692878
J Pediatr. 1980 Feb;96(2):316-8
6985958
Nat Immunol. 2011 Mar;12(3):189-94
21321588
J Biol Chem. 1984 May 10;259(9):5430-9
6371005
Sci STKE. 2003 Feb 18;2003(170):PL5
12591998
J Immunol. 1975 Dec;115(6):1650-6
1102606
J Exp Med. 1984 Oct 1;160(4):1247-52
6481304
J Cell Biol. 1997 Dec 1;139(5):1349-60
9382879
PLoS One. 2015 Apr 13;10(4):e0120341
25867529
Pediatr Allergy Immunol. 2007 Dec;18(8):643-51
18078418
Cytokine. 2005 Feb 7;29(3):135-40
15613281
J Cell Biol. 1999 Nov 1;147(3):577-88
10545501
Biol Neonate. 2003;83(2):107-12
12576754
Scand J Immunol. 1980;11(3):271-82
9537055
Curr Protoc Cell Biol. 2001 May;Chapter 12:Unit 12.1
18228315
Nat Rev Drug Discov. 2010 May;9(5):373-86
20431569
Pediatr Res. 1986 Apr;20(4):296-300
3703618
Methods Enzymol. 1988;162:198-214
3067051
J Cell Biol. 2002 Oct 14;159(1):91-102
12370241