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Impaired CD14-dependent and independent response of polymorphonuclear leukocytes in preterm infants
Philipp Henneke1, Inga Osmers, Karl Bauer
1Department of Pediatrics, Benjamin Franklin Medical Center, FU Medical School, Berlin, Germany. philipp.henneke@umassmed.edu
Unlabelled:
Preterm newborn infants are especially susceptible to Gram-negative sepsis that is associated with a lethality of up to 40%.
Aims:
We tested whether polymorphonuclear leukocytes (PMN) from preterm infants exhibit an impaired antibacterial response upon stimulation with lipopolysaccharide (LPS) from Escherichia coli when compared to full term newborns or adults.
Methods:
We studied the effect of LPS on the expression of the surface proteins CD11b and CD14 and the secretion of elastase by PMN from preterm infants, term infants and adults ex vivo.
Results:
We found a significantly reduced antibacterial activity of PMN from preterm infants upon stimulation with LPS as indicated by low surface expression of the adhesion molecule CD11b and the reduced secretion of PMN elastase. LPS-induced CD11b expression was dependent on binding of LPS to the surface protein CD14 as CD14 antibodies inhibited LPS dependent CD11b upregulation. Furthermore CD14 expression was lower on PMN from preterm infants than from adults. In addition, CD14 independent upregulation of CD11b in response to tumor necrosis factor (TNF-alpha), N-formyl peptides (FMLP) and phorbol ester (PMA) was impaired.
Conclusion:
PMN from preterm infants are distinctly hyporesponsive to LPS, which may explain the predisposition of these children to invasive disease due to gramnegative bacteria.