Plasma CD14 decreases monocyte responses to LPS by transferring cell-boundLPS to plasma lipoproteins

CD14, a myeloid cell-surface receptor and soluble plasma protein, binds LPS and other microbial molecules and initiates the innate immune response to bacterial invasion. The blood concentration of soluble CD14 (sCD14) increas es during the systemic response to infection. Although high sCD14 blood lev els have correlated with increased risk of dying from severe sepsis, sCD14 can diminish cell responses to LPS. We show here that in human serum, sCD14 increases the rate at which cell-bound LPS is released from the monocyte s urface and binds to plasma lipoproteins. This enhanced rate of LPS efflux i s associated with a significant reduction in the ability of monocytes to pr oduce cytokines in response to LPS. Serum from septic patients reduced the LPS-monocyte interaction by as much as tenfold, and depletion of sCD14 from the serum restored LPS-monocyte binding and release kinetics to near norma l levels. In serum from septic patients, monocyte-bound LPS also moved more rapidly into lipoproteins, which completely neutralized the biologic activ ity of the LPS that bound to them. In human plasma, sCD14 thus diminishes m onocyte responses to LPS by transferring cell-bound LPS to lipoproteins. St ress-related increases in plasma sCD14 levels may help prevent inflammatory responses within the blood.