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Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
Plasma CD14 decreases monocyte responses to LPS by transferring cell-bound LPS to plasma lipoproteins
R L Kitchens1, P A Thompson, S Viriyakosol
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113, USA. richard.kitchens@UTSouthwestern.edu
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.
Insights
Soluble CD14 (sCD14) in human serum enhances the release of lipopolysaccharide (LPS) from monocytes, reducing cytokine production. This mechanism may prevent excessive inflammation during sepsis.
Area of Science:
- Immunology
- Infectious Disease
Background:
- Soluble CD14 (sCD14) is a protein that binds microbial molecules like LPS, initiating innate immune responses.
- Elevated sCD14 levels are observed during sepsis, but its role in modulating cellular responses is complex.
Purpose of the Study:
- To investigate the mechanism by which sCD14 influences monocyte responses to LPS in human serum.
- To determine if sCD14 affects LPS binding, release, and subsequent cellular activation.
Main Methods:
- Studied the interaction of LPS with human monocytes in serum containing varying sCD14 concentrations.
- Measured LPS release from monocyte surfaces and subsequent binding to plasma lipoproteins.
- Assessed monocyte cytokine production in response to LPS.
Main Results:
- sCD14 significantly increased the rate of LPS release from monocytes into serum.
- This enhanced LPS efflux reduced monocyte cytokine production in response to LPS.
- Septic patient serum, rich in sCD14, markedly reduced LPS-monocyte interactions, with depleted sCD14 restoring normal kinetics.
- LPS bound to lipoproteins in septic serum was biologically inactivated.
Conclusions:
- sCD14 diminishes monocyte inflammatory responses to LPS by facilitating LPS transfer to lipoproteins.
- Increased sCD14 levels during sepsis may serve as a protective mechanism against overwhelming inflammation.
