Plasma CD14 decreases monocyte responses to LPS by transferring cell-bound LPS to plasma lipoproteins
Richard L. Kitchens, … , Grant E. O’Keefe, Robert S. Munford
Richard L. Kitchens, … , Grant E. O’Keefe, Robert S. Munford
Published August 1, 2001
Citation Information: J Clin Invest. 2001;108(3):485-493. https://doi.org/10.1172/JCI13139.
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Article

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

Abstract

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) increases during the systemic response to infection. Although high sCD14 blood levels 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 surface and binds to plasma lipoproteins. This enhanced rate of LPS efflux is associated with a significant reduction in the ability of monocytes to produce 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 normal levels. In serum from septic patients, monocyte-bound LPS also moved more rapidly into lipoproteins, which completely neutralized the biologic activity of the LPS that bound to them. In human plasma, sCD14 thus diminishes monocyte responses to LPS by transferring cell-bound LPS to lipoproteins. Stress-related increases in plasma sCD14 levels may help prevent inflammatory responses within the blood.

Authors

Richard L. Kitchens, Patricia A. Thompson, Suganya Viriyakosol, Grant E. O’Keefe, Robert S. Munford

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Sepsis serum accelerates the release of cell-bound LPS from monocytes. (...
Sepsis serum accelerates the release of cell-bound LPS from monocytes. (a) Time courses of [3H]LPS release from THP-1 cells were measured in undiluted serum as described in Methods. The total cell-associated [3H]LPS is shown as the percentage of that initially bound to the cells. The data from normal serum are means ± SD of 15 determinations from nine different normal donors (closed circles and dashed line). The data from the patients (14 samples from ten individuals) are shown individually by solid lines. The means of duplicate determinations are shown without symbols, and the ranges (data not shown) do not deviate more than 3% on the y-axis. (b) The analyses according to clinical groups were performed as in Figure 2b using data from the normal samples and 27 patient samples including those shown in a. The y-axis denotes the percentage of LPS released at the 15-minute time point.