Delineation of Lipopolysaccharide (LPS)-binding Sites on Hemoglobin

Bahl, Neha; Du, Ruijuan; Winarsih, Imelda; Ho, Bow; Tucker-Kellogg, Lisa; Tidor, Bruce; Ding, Jeak Ling

doi:10.1074/jbc.m111.245472

Cited by 31 publications

(21 citation statements)

References 38 publications

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“…heat-shock protein HMGB1) [24, 61, 68, 79–81]. Surface plasmon resonance revealed LPS binding sites are present on both the α and β globin chains of Hb [82]. Synthetic peptides representative of these putative ligand-binding regions targeted the lipid A moiety of LPS in vitro, and in doing so, disarmed the endotoxicity.…”

Section: The Oxygen-transport Proteinsmentioning

confidence: 99%

“…Synthetic peptides representative of these putative ligand-binding regions targeted the lipid A moiety of LPS in vitro, and in doing so, disarmed the endotoxicity. Binding of LPS and/or LTA induces a conformational switch in Hb that causes the structure to loosen somewhat and enable peroxidase activity [24, 82]. Methemoglobin (metHb) alone and in combination with LTA can be recognised by TLR-2 on the neutrophil plasma membrane [81].…”

Section: The Oxygen-transport Proteinsmentioning

confidence: 99%

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Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin

Coates

Decker

2016

Cell. Mol. Life Sci.

129

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It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dynamics in innate immunity, and to impress upon the reader the multi-functionality of these ancient proteins on the basis of their structures. In this context, erythrocyte–pathogen antibiosis and the immune competences of various erythroid cells are compared across diverse taxa.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-016-2326-7) contains supplementary material, which is available to authorized users.

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Section: The Oxygen-transport Proteinsmentioning

confidence: 99%

Section: The Oxygen-transport Proteinsmentioning

confidence: 99%

Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin

Coates

Decker

2016

Cell. Mol. Life Sci.

129

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“…The synergism between Hb and LPS is often attributed to Hb binding to LPS, causing disaggregation of LPS multimers and enhancing the exposure to LPS lipid A moieties [21,22]. Previous studies have also suggested that Hb augments LPS-induced TNF-alpha response in cultured monocytes and in vivo , an effect thought to contribute to the synergistic toxicity of Hb and LPS [23,24].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Hb Enhances Cardiac Toxicity in Endotoxemic Guinea Pigs: Protective Role of Haptoglobin

Baek

Zhang

Williams

et al. 2014

Toxins

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Endotoxemia plays a major causative role in the myocardial injury and dysfunction associated with sepsis. Extracellular hemoglobin (Hb) has been shown to enhance the pathophysiology of endotoxemia. In the present study, we examined the myocardial pathophysiology in guinea pigs infused with lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, and purified Hb. We also examined whether the administration of the Hb scavenger haptoglobin (Hp) could protect against the effects observed. Here, we show that Hb infusion following LPS administration, but not either insult alone, increased myocardial iron deposition, heme oxygenase-1 expression, phagocyte activation and infiltration, as well as oxidative DNA damage and apoptosis assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunostaining, respectively. Co-administration of Hp significantly attenuated the myocardial events induced by the combination of LPS and Hb. These findings may have relevant therapeutic implications for the management of sepsis during concomitant disease or clinical interventions associated with the increased co-exposures to LPS and Hb, such as trauma, surgery or massive blood transfusions.

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“…5). In comparison to other LPS studies in the SPR literature, our assays were performed using a stringent flow rate (i.e., 25 l/min, like that used by Bahl et al [58]) and avoided the use of complicating carrier proteins, such as BSA, in the running buffer (59). Like the high-affinity interaction reported by Bahl et al (58) that mapped specific LPS-binding hot spots on hemoglobin, the slow dissociation kinetics that we observed suggest that the PGA-LPS interaction is not weak (e.g., there was no immediate return of the SPR signal to the baseline at 70 to 120 s in Fig.…”

Section: Discussionmentioning

confidence: 99%

Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae

et al. 2016

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c Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an Oantigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA.A ctinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and is the causative agent of porcine pleuropneumonia, a disease causing important economic losses to the swine industry worldwide (1). Several virulence factors of A. pleuropneumoniae have been identified. These factors include the Apx toxins, iron uptake systems, and surface polysaccharides. These polysaccharides are divided into three categories: the lipopolysaccharides (LPS), the capsular polysaccharides (CPS), and the poly-N-acetyl-D-glucosamine polymer (PGA) present in the biofilm matrix (2-4).LPS are large biomolecules composed of three well-defined regions: (i) lipid A, anchored in the outer membrane; (ii) the core oligosaccharide; and (iii) the O antigen, a polysaccharide consisting of repeating units. Altman and coworkers described the structure of the A. pleuropneumoniae serotype 1 O antigen to be branched tetrasaccharide repeating units composed of two Lrhamnopyranosyl residues, one D-glycopyranosyl residue, and one 2-acetamido-2-deoxy-D-glucose residue (5). The LPS inner core oligosaccharide is relatively conserved among A. pleuropneumoniae serotype 1, 2, 5a, and 5b strains and is composed of 2-keto-3-deoxyoctulosonic acid and heptose, whereas the outer core oligosaccharide is variable among serotypes and is generally made of a variable number of branching hexoses (6). The A. pleuropneumoniae LPS has been identified to b...

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Delineation of Lipopolysaccharide (LPS)-binding Sites on Hemoglobin

Cited by 31 publications

References 38 publications

Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin

Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin

Extracellular Hb Enhances Cardiac Toxicity in Endotoxemic Guinea Pigs: Protective Role of Haptoglobin

Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae

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