Extracellular release of bactericidal/permeability-increasing protein in newborn infants.
Upon activation, polymorphonuclear leucocytes (PMN) release bactericidal/permeability-increasing protein, (BPI) from their azurophil granules. BPI selectively binds to the lipopolysaccharide (LPS) on gram-negative bacteria and induces their death. This study examined plasma BPI concentration levels in healthy newborns and in newborns with clinical sepsis, and the ability of PMN from preterm and term infants to release BPI. We also studied the release of myeloperoxidase (MPO), and the surface expression of adhesion molecule CD11b on PMN. In infants with clinical sepsis, plasma BPI concentration was higher, 27.8 microg/L [8.6-883; median (range)] (n = 11), than in healthy term infants 8.9 microg/L (3.9-179) (n = 17), and in adults 7.3 microg/L (0.7 -18.4) (n = 15); p = 0.014, Kruskal-Wallis. In preterm infants (n = 8), the ability of PMN to release BPI in vitro after stimulation with PMA was 8.8, in term infants it was 15.9 (n = 29; p > 0.05 vs. preterm infants) and in adults 23.4 ng/10(6) PMN (n = 15; p = 0.024 and p > 0.05 vs. preterm and term infants, respectively). The corresponding values of MPO were 20.0 ng/10(6) (11.3-46.7) in preterms, 19.0 ng/10(6) (2.2-223.7) in terms, and 27.8 ng/10(6) (9.1-80.7) in adults; p = 0.67 between groups. In infants with clinical sepsis, CD11b level was higher, 292 RFU (234-403) than the basal CD11b expression levels in healthy newborn infants, 116 RFU (76-145); P = 0.0001. FMLP-stimulated PMN CD11b expressions in preterm cord blood, 1071 RFU (552-1286) and in term cord blood, 918 (567-1472) were on the same level, but lower than that in adult blood, 1592 (973-1946); p < 0.001, ANOVA. Our findings suggest that in preterm infants the ability to release BPI is lower than in adults and term infants. These findings suggest that premature neonates have an impaired ability to mobilize BPI, possibly contributing to their marked susceptibility to infections with Gram-negative bacteria.
Nupponen
Irmeli
I
Hospital for Children and Adolescents, FIN-00029 University of Helsinki, Finland. irmeli.nupponen@kolumbus.fi
Turunen
Riikka
R
Nevalainen
Timo
T
Peuravuori
Heikki
H
Pohjavuori
Maija
M
Repo
Heikki
H
Andersson
Sture
S
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000276:immunology* / Q000378:metabolism*; D015550:Cell Degranulation / Q000276:immunology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007958:Leukocyte Count; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D008565:Membrane Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase