CD14-INDEPENDENT RESPONSES TO LPS REQUIRE A SERUM FACTOR THAT IS ABSENT FROM NEONATES

Monocytes/macrophages and neutrophils can respond to endotoxin via a h igh-affinity receptor (CD14), requiring low levels of LPS (<1 ng/ml) a s 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 c ytokines, such as TNF-alpha, and the up-regulation of various other ef fector molecules. To further define the activation of cells by LPS via a pathway that does not involve CD14, we have used an experimental mo del that distinguishes CD14-dependent from CD14-independent responses using saturating amounts of an anti-CD14 Ab to block the CD14-dependen t response. Analysis of the ability of various individuals to respond to LPS via both the CD14-dependent and CD14-independent pathways shows that adults can respond via both pathways; furthermore, in the presen ce of 100 ng of LPS/ml, the primary response is CD14 independent. In c ontrast to the response by adults, neonates can only respond via the C D14-dependent pathway. Further analysis has shown that the CD14-indepe ndent pathway requires a non-CD14 plasma protein present in adult plas ma that is either missing or nonfunctional in neonate (card) plasma.