Serum proteins modulate lipopolysaccharide and lipoteichoic acid-induced activation and contribute to the clinical outcome of sepsis

Abstract

Keywords: sepsis, serum proteins, LPS, LTABacterial cell wall components, such LPS and LTA, are potent initiators of an inflammatory response that can lead to septic shock. The advances in the past were centered around membrane-bound receptors and intracellular events, but our understanding of the initial interactions of these bacterial components with serum proteins as they enter the bloodstream remain unclear. In this study we identified several serum proteins, which are involved in the innate recognition of bacterial products. Using affinity chromatography and mass spectrometry we performed proteomic analysis of LPS-and LTA-binding serum proteins. We isolated proteins from normal serum that can interact with LPS and LTA. Fluorescent binding experiments and cytokine assays revealed that serum proteins, such as apolipoprotein, LDL, transferrin and holotransferrin could neutralize LPS/LTA binding as well as the subsequent inflammatory response, suggesting that serum proteins modulate LPS/LTA-induced responses. When compared with the proteomic profile of serum from septic patients it was shown that these proteins were in lower abundance. Investigation of serum proteins in 25 critically ill patients with a mortality rate of 40% showed statistically higher levels of these proteins in survivors.Patients surviving sepsis had statistically significant higher levels of apolipoprotein, albumin, LDL, transferrin and holotransferrin than individuals that succumbed, suggesting that these proteins have an inhibitory effect on LPS/LTAinduced inflammatory responses and in their absence there might be an augmented inflammatory response in sepsis.

Structural Stability and Viability of Microencapsulated Probiotic Bacteria: A Review

“…Because this interaction results in cell wall distortion‐disruption and exposes bacteria to osmotic shock, such cationic polysaccharides are considered potent (<200 ppm) antimicrobials against Gram‐positive bacteria, such as Staphylococcus aureus and Listeria monocytogenes , and, at higher concentrations, against Lactobacilli (Goy and others ), while oleoyl‐chitosan nanoparticles (a more lipophilic particle) inhibit Escherichia coli and S. aureus by damaging the cell membrane and other intracellular targets (Xing and others ). Triantafilou and others () demonstrated that blood proteins such as apolipoproteins, LDL, and transferrin inactivate LTA, reducing its proinflammatory potential. This finding may indicate that dietary proteins can also bind to LTA, reducing or facilitating bacterial release within the GI tract.…”

Modulatory effect of lipopolysaccharide on immune‐related gene expression and serum protein fractionation in grey mullet,Mugil cephalus

“…Liu, Yu, Chai, and Zhu (2012) suggested that transferrin has a role in activating the antimicrobial activity of macrophages or inducing strong pro-inflammatory responses. More importantly, transferrin was found as a major lipopolysaccharide binding protein, acting as a neutralizing agent (Berger, Schleich, Seidelmann, & Beger, 1991;Triantafilou et al, 2012), suggesting its inhibitory effect on LPSinduced inflammatory responses. Transferrin significantly evoked the killing activity of goldfish macrophages subjected to different pathogens or pathogen products including LPS (Stafford & Belosevic, 2003).…”

HMGB1 Binds to Lipoteichoic Acid and Enhances TNF-a and IL-6 Production through HMGB1-Mediated Transfer of Lipoteichoic Acid to CD14 and TLR2

“…There are many LTA-binding proteins, as follows: LBP, CD14, mannose-binding protein, L-ficolin, albumin [6,31,32,33], apolipoproteins A and C [34], transferrin and hemoglobin [35,36], high- and low-density lipoproteins [37], hemoglobin subunits α and β and S100A9 and SPLUNC2 [38]. Until now, however, LBP was the only molecule known to mediate the transfer of LTA to CD14 to enhance the inflammatory response.…”