CD14-independent responses to LPS require a serum factor that is absent from neonates.
Monocytes/macrophages and neutrophils can respond to endotoxin via a high-affinity receptor (CD14), requiring low levels of LPS (< 1 ng/ml) as well as through another pathway(s) that requires high levels of LPS (> 10 ng/ml). Both pathways result in the secretion of high levels of cytokines, such as TNF-alpha, and the up-regulation of various other effector molecules. To further define the activation of cells by LPS via a pathway that does not involve CD14, we have used an experimental model that distinguishes CD14-dependent from CD14-independent responses using saturating amounts of an anti-CD14 Ab to block the CD14-dependent response. Analysis of the ability of various individuals to respond to LPS via via both the CD14-dependent and CD14-independent pathways shows that adults can respond via both pathways; furthermore, in the presence of 100 ng of LPS/ml, the primary response is CD14 independent. In contrast to the response by adults, neonates can only respond via the CD14-dependent pathway. Further analysis has shown that the CD14-independent pathway requires a non-CD14 plasma protein present in adult plasma that is either missing or nonfunctional in neonate (cord) plasma.
Cohen
L
L
Department of Pediatrics, North Shore University Hospital/Cornell University Medical College, Manhasset, NY 11030, USA.
Haziot
A
A
Shen
D R
DR
Lin
X Y
XY
Sia
C
C
Harper
R
R
Silver
J
J
Goyert
S M
SM
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001798:Blood Proteins / Q000276:immunology*; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides