ENDOTOXIN TOLERANCE IS INDUCED IN CHINESE-HAMSTER OVARY CELL-LINES EXPRESSING HUMAN CD14

Changes in patterns of gene induction by myeloid lineage cells followi ng multiple exposures to endotoxin (lipopolysaccharide; LPS) is a feat ure of LPS tolerance, To further understand the mechanism of this phen omenon we describe studies using stably transfected Chinese hamster ov ary cell lines that express human CD14 (CHO-hCD14). Using NF-KB activa tion as a measure of LPS-induced cell activation we show that a single treatment with LPS renders CHO-hCD14 cells tolerant to subsequent cha llenge with LPS, but not with other stimuli such as tumor necrosis fac tor. Tolerance may result from the induction of gene(s) that control L PS-induced signaling pathways and here we suggest that such genes may be found in the group of immediate, early response genes characterized by the protein phosphatase 3CH134. The CHO-hCD14 cell lines provide a novel model system to further explore the mechanism of endotoxin tole rance.