The Journal of Immunology, Vol 155, Issue 11 5337-5342, Copyright © 1995 by American Association of Immunologists

ARTICLES

CD14-independent responses to LPS require a serum factor that is absent from neonates

L Cohen, A Haziot, DR Shen, XY Lin, C Sia, R Harper, J Silver and SM Goyert
Department of Pediatrics, North Shore University Hospital/Cornell University Medical College, Manhasset, NY 11030, USA.

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.

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