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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Septicemia | Review

Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis

Authors: Min Wang, Jun Feng, Daixing Zhou, Junshuai Wang

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Background

Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide or other foreign debris in the bloodstream. Endothelial cells are able to recognize the presence of LPS and recruit specific adaptor proteins to the membrane domains of TLR4, thereby initiating an intracellular signaling cascade. However, lipopolysaccharide binding to endothelial cells induces endothelial activation and even damage, manifested by the expression of proinflammatory cytokines and adhesion molecules that lead to sepsis.

Main findings

LPS is involved in both local and systemic inflammation, activating both innate and adaptive immunity. Translocation of lipopolysaccharide into the circulation causes endotoxemia. Endothelial dysfunction, including exaggerated inflammation, coagulopathy and vascular leakage, may play a central role in the dysregulated host response and pathogenesis of sepsis. By discussing the many strategies used to treat sepsis, this review attempts to provide an overview of how lipopolysaccharide induces the ever more complex syndrome of sepsis and the potential for the development of novel sepsis therapeutics.

Conclusions

To reduce patient morbidity and mortality, preservation of endothelial function would be central to the management of sepsis.

Graphical Abstract

Literature
1.
Minasyan H. Sepsis and septic shock: pathogenesis and treatment perspectives. J Crit Care. 2017;40:229–42.PubMed
2.
Cavaillon JM. Exotoxins and endotoxins: inducers of inflammatory cytokines. Toxicon. 2018;149:45–53.PubMed
3.
Sheehan JR, Sadlier C, O’Brien B. Bacterial endotoxins and exotoxins in intensive care medicine. BJA Educ. 2022;22(6):224–30.PubMedPubMedCentral
4.
Holmes CL, Anderson MT, Mobley HLT, Bachman MA. Pathogenesis of gram-negative bacteremia. Clin Microbiol Rev. 2021;34(2):10.
5.
Kumar V. Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Front Immunol. 2020;11:1722.PubMedPubMedCentral
6.
Dickson K, Lehmann C. Inflammatory response to different toxins in experimental sepsis models. Int J Mol Sci. 2019;20(18):4341.PubMedPubMedCentral
7.
Caffaratti C, Plazy C, Mery G, Tidjani AR, Fiorini F, Thiroux S, et al. What we know so far about the metabolite-mediated microbiota-intestinal immunity dialogue and how to hear the sound of this crosstalk. Metabolites. 2021;11(6):406.PubMedPubMedCentral
8.
Zhao Y, Arce-Gorvel V, Conde-Alvarez R, Moriyon I, Gorvel JP. Vaccine development targeting lipopolysaccharide structure modification. Microbes Infect. 2018;20(9–10):455–60.PubMed
9.
Mazarati A, Medel-Matus JS, Shin D, Jacobs JP, Sankar R. Disruption of intestinal barrier and endotoxemia after traumatic brain injury: implications for post-traumatic epilepsy. Epilepsia. 2021;62(6):1472–81.PubMed
10.
Tanaka S, Couret D, Tran-Dinh A, Duranteau J, Montravers P, Schwendeman A, et al. High-density lipoproteins during sepsis: from bench to bedside. Crit Care. 2020;24(1):134.PubMedPubMedCentral
11.
Ioanna Z, Katerina B, Irene A. Immunotherapy-on-chip against an experimental sepsis model. Inflammation. 2021;44(6):2333–45.PubMed
12.
Feng J, Liu L, He Y, Wang M, Zhou D, Wang J. Novel insights into the pathogenesis of virus-induced ARDS: review on the central role of the epithelial-endothelial barrier. Expert Rev Clin Immunol. 2021;17(9):991–1001.PubMed
13.
Smiechowicz J. The rationale and current status of endotoxin adsorption in the treatment of septic shock. J Clin Med. 2022;11(3):619.PubMedPubMedCentral
14.
Perez-Hernandez EG, Delgado-Coello B, Luna-Reyes I, Mas-Oliva J. New insights into lipopolysaccharide inactivation mechanisms in sepsis. Biomed Pharmacother. 2021;141:111890.PubMed
15.
Pussinen PJ, Kopra E, Pietiainen M, Lehto M, Zaric S, Paju S, et al. Periodontitis and cardiometabolic disorders: the role of lipopolysaccharide and endotoxemia 2000. Periodontol. 2022;89(1):19–40.
16.
Venkataranganayaka Abhilasha K, Kedihithlu MG. Bacterial lipoproteins in sepsis. Immunobiology. 2021;226(5):152128.PubMed
17.
Nova Z, Skovierova H, Calkovska A. Alveolar-capillary membrane-related pulmonary cells as a target in endotoxin-induced acute lung injury. Int J Mol Sci. 2019;20(4):831.PubMedPubMedCentral
18.
Sun HJ, Wu ZY, Nie XW, Bian JS. Role of endothelial dysfunction in cardiovascular diseases: the link between inflammation and hydrogen sulfide. Front Pharmacol. 2019;10:1568.PubMed
19.
Claser C, Nguee SYT, Balachander A, Wu Howland S, Becht E, Gunasegaran B, et al. Lung endothelial cell antigen cross-presentation to CD8(+)T cells drives malaria-associated lung injury. Nat Commun. 2019;10(1):4241.PubMedPubMedCentral
20.
Sanz Codina M, Zeitlinger M. Biomarkers predicting tissue pharmacokinetics of antimicrobials in sepsis: a review. Clin Pharmacokinet. 2022;61:593.PubMedPubMedCentral
21.
Grondman I, Pirvu A, Riza A, Ioana M, Netea MG. Biomarkers of inflammation and the etiology of sepsis. Biochem Soc Trans. 2020;48(1):1–14.PubMed
22.
Peng X, Luo Z, He S, Zhang L, Li Y. Blood-brain barrier disruption by lipopolysaccharide and sepsis-associated encephalopathy. Front Cell Infect Microbiol. 2021;11:768108.PubMedPubMedCentral
23.
Klein G, Raina S. Regulated assembly of LPS, its structural alterations and cellular response to LPS defects. Int J Mol Sci. 2019;20(2):356.PubMedPubMedCentral
24.
Farhana A, Khan YS. Biochemistry, lipopolysaccharide. Saint Petersburg: StatPearls Treasure Island (FL); 2022.
25.
Zamyatina A, Heine H. Lipopolysaccharide recognition in the crossroads of TLR4 and caspase-4/11 mediated inflammatory pathways. Front Immunol. 2020;11:585146.PubMedPubMedCentral
26.
Liao FH, Wu TH, Huang YT, Lin WJ, Su CJ, Jeng US, et al. Subnanometer gold clusters adhere to lipid a for protection against endotoxin-induced sepsis. Nano Lett. 2018;18(5):2864–9.PubMed
27.
28.
Maciejewska A, Bednarczyk B, Lugowski C, Lukasiewicz J. Structural studies of the lipopolysaccharide isolated from Plesiomonas shigelloides O22:H3 (CNCTC 90/89). Int J Mol Sci. 2020;21(18):6788.PubMedPubMedCentral
29.
Chaiwut R, Kasinrerk W. Very low concentration of lipopolysaccharide can induce the production of various cytokines and chemokines in human primary monocytes. BMC Res Notes. 2022;15(1):42.PubMedPubMedCentral
30.
Ohnishi T, Muroi M, Tanamoto K. The lipopolysaccharide-recognition mechanism in cells expressing TLR4 and CD14 but lacking MD-2. FEMS Immunol Med Microbiol. 2007;51(1):84–91.PubMed
31.
Zdorovenko EL, Besarab NV, Shashkov AS, Novik GI, Shirokov AA, Burov AM, et al. Investigation of O-polysaccharides from bacterial strains of Pseudomonas genus as potential receptors of bacteriophage BIM BV-45. Int J Biol Macromol. 2018;118(Pt A):1065–72.PubMed
32.
Jiao Y, Li W, Wang W, Tong X, Xia R, Fan J, et al. Platelet-derived exosomes promote neutrophil extracellular trap formation during septic shock. Crit Care. 2020;24(1):380.PubMedPubMedCentral
33.
Anderson JA, Loes AN, Waddell GL, Harms MJ. Tracing the evolution of novel features of human Toll-like receptor 4. Protein Sci. 2019;28(7):1350–8.PubMedPubMedCentral
34.
Cochet F, Peri F. The role of carbohydrates in the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signalling. Int J Mol Sci. 2017;18(11):2318.PubMedPubMedCentral
35.
Kuzmich NN, Sivak KV, Chubarev VN, Porozov YB, Savateeva-Lyubimova TN, Peri F. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis. Vaccines. 2017;5(4):34.PubMedPubMedCentral
36.
37.
Su L, Athamna M, Wang Y, Wang J, Freudenberg M, Yue T, et al. Sulfatides are endogenous ligands for the TLR4-MD-2 complex. Proc Natl Acad Sci U S A. 2021;118(30):e2105316118.PubMedPubMedCentral
38.
Ryu JK, Kim SJ, Rah SH, Kang JI, Jung HE, Lee D, et al. Reconstruction of LPS transfer cascade reveals structural determinants within LBP, CD14, and TLR4-MD2 for efficient LPS recognition and transfer. Immunity. 2017;46(1):38–50.PubMed
39.
Gabarin RS, Li M, Zimmel PA, Marshall JC, Li Y, Zhang H. Intracellular and extracellular lipopolysaccharide signaling in sepsis: avenues for novel therapeutic strategies. J Innate Immun. 2021;13(6):323–32.PubMedPubMedCentral
40.
Ciesielska A, Matyjek M, Kwiatkowska K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol Life Sci. 2021;78(4):1233–61.PubMed
41.
Ren Y, Ichinose T, He M, Youshida S, Nishikawa M, Sun G. Co-exposure to lipopolysaccharide and desert dust causes exacerbation of ovalbumin-induced allergic lung inflammation in mice via TLR4/MyD88-dependent and -independent pathways. Allergy Asthma Clin Immunol. 2019;15:82.PubMedPubMedCentral
42.
Xu D, Zhao M, Song Y, Song J, Huang Y, Wang J. Novel insights in preventing gram-negative bacterial infection in cirrhotic patients: review on the effects of GM-CSF in maintaining homeostasis of the immune system. Hepatol Int. 2015;9(1):28–34.PubMed
43.
Firmal P, Shah VK, Chattopadhyay S. Insight into TLR4-mediated immunomodulation in normal pregnancy and related disorders. Front Immunol. 2020;11:807.PubMedPubMedCentral
44.
Yi YS. Caspase-11 non-canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage-mediated inflammatory responses. Immunology. 2017;152(2):207–17.PubMedPubMedCentral
45.
Sabnis A, Hagart KL, Klockner A, Becce M, Evans LE, Furniss RCD, et al. Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane. Elife. 2021;10:e65836.PubMedCentral
46.
Paria A, Makesh M, Chaudhari A, Purushothaman CS, Rajendran KV. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in Asian seabass, Lates calcarifer: cloning, ontogeny and expression analysis following bacterial infection or ligand stimulation. Fish Shellfish Immunol. 2018;79:153–62.PubMed
47.
Downs KP, Nguyen H, Dorfleutner A, Stehlik C. An overview of the non-canonical inflammasome. Mol Aspects Med. 2020;76:100924.PubMed
48.
Zhao J, Liu Z, Chang Z. Lipopolysaccharide induces vascular endothelial cell pyroptosis via the SP1/RCN2/ROS signaling pathway. Eur J Cell Biol. 2021;100(4):151164.PubMed
49.
Lagrange B, Benaoudia S, Wallet P, Magnotti F, Provost A, Michal F, et al. Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and functions differently from murine caspase-11. Nat Commun. 2018;9(1):242.PubMedPubMedCentral
50.
Chen S, Yang D, Wen Y, Jiang Z, Zhang L, Jiang J, et al. Dysregulated hemolysin liberates bacterial outer membrane vesicles for cytosolic lipopolysaccharide sensing. PLoS Pathog. 2018;14(8):e1007240.PubMedPubMedCentral
51.
Pfalzgraff A, Weindl G. Intracellular lipopolysaccharide sensing as a potential therapeutic target for sepsis. Trends Pharmacol Sci. 2019;40(3):187–97.PubMed
52.
Li X, Zhong CQ, Yin Z, Qi H, Xu F, He Q, et al. Data-driven modeling identifies TIRAP-independent MyD88 activation complex and myddosome assembly strategy in LPS/TLR4 signaling. Int J Mol Sci. 2020;21(9):3061.PubMedPubMedCentral
53.
Moretti J, Blander JM. Increasing complexity of NLRP3 inflammasome regulation. J Leukoc Biol. 2021;109(3):561–71.PubMed
54.
Moriyama K, Nishida O. Targeting cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns in sepsis via blood purification. Int J Mol Sci. 2021;22(16):8882.PubMedPubMedCentral
55.
Pons S, Arnaud M, Loiselle M, Arrii E, Azoulay E, Zafrani L. Immune consequences of endothelial cells’ activation and dysfunction during sepsis. Crit Care Clin. 2020;36(2):401–13.PubMed
56.
Joffre J, Hellman J, Ince C, Ait-Oufella H. Endothelial responses in sepsis. Am J Respir Crit Care Med. 2020;202(3):361–70.PubMed
57.
Ito T, Kakuuchi M, Maruyama I. Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation. Crit Care. 2021;25(1):95.PubMedPubMedCentral
58.
Kruger-Genge A, Blocki A, Franke RP, Jung F. Vascular endothelial cell biology: an update. Int J Mol Sci. 2019;20(18):4411.PubMedPubMedCentral
59.
Osburn WO, Smith K, Yanek L, Amat-Alcaron N, Thiemann DR, Cox AL, et al. Markers of endothelial cell activation are associated with the severity of pulmonary disease in COVID-19. PLoS ONE. 2022;17(5):e0268296.PubMedPubMedCentral
60.
Fernandez S, Palomo M, Molina P, Diaz-Ricart M, Escolar G, Tellez A, et al. Progressive endothelial cell damage in correlation with sepsis severity. defibrotide as a contender. J Thromb Haemost. 2021;19(8):1948–58.PubMed
61.
Parikh SM. Targeting Tie2 and the host vascular response in sepsis. Sci Transl Med. 2016;8(335):335fs9.PubMed
62.
Maneta E, Aivalioti E, Tual-Chalot S, Emini Veseli B, Gatsiou A, Stamatelopoulos K, et al. Endothelial dysfunction and immunothrombosis in sepsis. Front Immunol. 2023;14:1144229.PubMedPubMedCentral
63.
Zhang YY, Ning BT. Signaling pathways and intervention therapies in sepsis. Signal Transduct Target Ther. 2021;6(1):407.PubMedPubMedCentral
64.
Barichello T, Generoso JS, Singer M, Dal-Pizzol F. Biomarkers for sepsis: more than just fever and leukocytosis-a narrative review. Crit Care. 2022;26(1):14.PubMedPubMedCentral
65.
Tomaskova V, Mytnikova A, Hortova Kohoutkova M, Mrkva O, Skotakova M, Sitina M, et al. Prognostic value of soluble endoglin in patients with septic shock and severe COVID-19. Front Med. 2022;9:972040.
66.
Root-Bernstein R. Innate receptor activation patterns involving TLR and NLR synergisms in COVID-19, ALI/ARDS and sepsis cytokine storms: a review and model making novel predictions and therapeutic suggestions. Int J Mol Sci. 2021;22(4):2108.PubMedPubMedCentral
67.
Shao Y, Saredy J, Yang WY, Sun Y, Lu Y, Saaoud F, et al. Vascular endothelial cells and innate immunity. Arterioscler Thromb Vasc Biol. 2020;40(6):e138–52.PubMedPubMedCentral
68.
Dayang EZ, Plantinga J, Ter Ellen B, van Meurs M, Molema G, Moser J. Identification of LPS-activated endothelial subpopulations with distinct inflammatory phenotypes and regulatory signaling mechanisms. Front Immunol. 2019;10:1169.PubMedPubMedCentral
69.
Kumar V. Inflammation research sails through the sea of immunology to reach immunometabolism. Int Immunopharmacol. 2019;73:128–45.PubMed
70.
Andersson U, Ottestad W, Tracey KJ. Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19? Mol Med. 2020;26(1):42.PubMedPubMedCentral
71.
Karbian N, Abutbul A, El-Amore R, Eliaz R, Beeri R, Reicher B, et al. Apoptotic cell therapy for cytokine storm associated with acute severe sepsis. Cell Death Dis. 2020;11(7):535.PubMedPubMedCentral
72.
Santambrogio L, Berendam SJ, Engelhard VH. The antigen processing and presentation machinery in lymphatic endothelial cells. Front Immunol. 2019;10:1033.PubMedPubMedCentral
73.
Pais TF, Penha-Goncalves C. Brain endothelium: the innate immunity response hypothesis in cerebral malaria pathogenesis. Front Immunol. 2018;9:3100.PubMed
74.
Rajaee A, Barnett R, Cheadle WG. Pathogen- and danger-associated molecular patterns and the cytokine response in sepsis. Surg Infect. 2018;19(2):107–16.
75.
Jacobi J. The pathophysiology of sepsis-2021 update: Part 1, immunology and coagulopathy leading to endothelial injury. Am J Health Syst Pharm. 2022;79(5):329–37.PubMed
76.
Kazune S, Caica A, Volceka K, Suba O, Rubins U, Grabovskis A. Relationship of mottling score, skin microcirculatory perfusion indices and biomarkers of endothelial dysfunction in patients with septic shock: an observational study. Crit Care. 2019;23(1):311.PubMedPubMedCentral
77.
Muller RB, Ostrowski SR, Haase N, Wetterslev J, Perner A, Johansson PI. Markers of endothelial damage and coagulation impairment in patients with severe sepsis resuscitated with hydroxyethyl starch 130/0.42 vs ringer acetate. J Crit Care. 2016;32:16–20.PubMed
78.
Leite AR, Borges-Canha M, Cardoso R, Neves JS, Castro-Ferreira R, Leite-Moreira A. Novel biomarkers for evaluation of endothelial dysfunction. Angiology. 2020;71(5):397–410.PubMed
79.
Karki R, Kanneganti TD. The “cytokine storm”: molecular mechanisms and therapeutic prospects. Trends Immunol. 2021;42(8):681–705.PubMedPubMedCentral
80.
Krakauer T. Inflammasomes, autophagy, and cell death: the trinity of innate host defense against intracellular bacteria. Mediators Inflamm. 2019;2019:2471215.PubMedPubMedCentral
81.
Barichello T, Generoso JS, Collodel A, Petronilho F, Dal-Pizzol F. The blood-brain barrier dysfunction in sepsis. Tissue Barriers. 2021;9(1):1840912.PubMed
82.
David S, Mukherjee A, Ghosh CC, Yano M, Khankin EV, Wenger JB, et al. Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis*. Crit Care Med. 2012;40(11):3034–41.PubMedPubMedCentral
83.
Drost CC, Rovas A, Kusche-Vihrog K, Van Slyke P, Kim H, Hoang VC, et al. Tie2 activation promotes protection and reconstitution of the endothelial glycocalyx in human sepsis. Thromb Haemost. 2019;119(11):1827–38.PubMed
84.
Schonemann-Lund M, Itenov TS, Larsson JE, Lindegaard B, Johansson PI, Bestle MH. Endotheliopathy is associated with slower liberation from mechanical ventilation: a cohort study. Crit Care. 2022;26(1):33.PubMedPubMedCentral
85.
Bonaventura A, Vecchie A, Dagna L, Martinod K, Dixon DL, Van Tassell BW, et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol. 2021;21(5):319–29.PubMedPubMedCentral
86.
Khakpour S, Wilhelmsen K, Hellman J. Vascular endothelial cell Toll-like receptor pathways in sepsis. Innate Immun. 2015;21(8):827–46.PubMed
87.
Zhang G, Cai Q, Zhou H, He C, Chen Y, Zhang P, et al. OxLDL/beta2GPI/antibeta2GPI Ab complex induces inflammatory activation via the TLR4/NFkappaB pathway in HUVECs. Mol Med Rep. 2021;23(2):1.PubMed
88.
Li R, Chinnathambi A, Alharbi SA, Shair OHM, Veeraraghavan VP, Surapaneni KM, et al. Anti-inflammatory effects of rhaponticin on LPS-induced human endothelial cells through inhibition of MAPK/NF-kappabeta signaling pathways. J Biochem Mol Toxicol. 2021;35(5):e22733.PubMed
89.
Dayang EZ, Luxen M, Kuiper T, Yan R, Rangarajan S, van Meurs M, et al. Pharmacological inhibition of focal adhesion kinase 1 (FAK1) and anaplastic lymphoma kinase (ALK) identified via kinome profile analysis attenuates lipopolysaccharide-induced endothelial inflammatory activation. Biomed Pharmacother. 2021;133:111073.PubMed
90.
Fereydouni Z, Amirinezhad Fard E, Mansouri K, Mohammadi Motlagh HR, Mostafaie A. Saponins from Tribulus terrestris L. extract down-regulate the expression of ICAM-1, VCAM-1 and E-selectin in human endothelial cell lines. Int J Mol Cell Med. 2020;9(1):73–83.PubMedPubMedCentral
91.
Jin K, Luo Z, Zhang B, Pang Z. Biomimetic nanoparticles for inflammation targeting. Acta Pharm Sin B. 2018;8(1):23–33.PubMed
92.
Janga H, Cassidy L, Wang F, Spengler D, Oestern-Fitschen S, Krause MF, et al. Site-specific and endothelial-mediated dysfunction of the alveolar-capillary barrier in response to lipopolysaccharides. J Cell Mol Med. 2018;22(2):982–98.PubMed
93.
Leligdowicz A, Chun LF, Jauregui A, Vessel K, Liu KD, Calfee CS, et al. Human pulmonary endothelial cell permeability after exposure to LPS-stimulated leukocyte supernatants derived from patients with early sepsis. Am J Physiol Lung Cell Mol Physiol. 2018;315(5):L638–44.PubMedPubMedCentral
94.
Pape T, Hunkemoller AM, Kumpers P, Haller H, David S, Stahl K. Targeting the “sweet spot” in septic shock—A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2. Matrix Biol Plus. 2021;12:100095.PubMedPubMedCentral
95.
Fernandez-Sarmiento J, Salazar-Pelaez LM, Carcillo JA. The endothelial Glycocalyx: a fundamental determinant of vascular permeability in sepsis. Pediatr Crit Care Med. 2020;21(5):e291–300.PubMedPubMedCentral
96.
Adams JA, Uryash A, Lopez JR. Non-invasive pulsatile shear stress modifies endothelial activation; a narrative review. Biomedicines. 2022;10(12):3050.PubMedPubMedCentral
97.
He L, Zhang CL, Chen Q, Wang L, Huang Y. Endothelial shear stress signal transduction and atherogenesis: from mechanisms to therapeutics. Pharmacol Ther. 2022;235:108152.PubMed
98.
Eckert D, Rapp F, Tsedeke AT, Molendowska J, Lehn R, Langhans M, et al. ROS- and radiation source-dependent modulation of leukocyte adhesion to primary microvascular endothelial cells. Cells. 2021;11(1):72.PubMedPubMedCentral
99.
Claesson-Welsh L, Dejana E, McDonald DM. Permeability of the endothelial barrier: identifying and reconciling controversies. Trends Mol Med. 2021;27(4):314–31.PubMed
100.
Moccia F, Negri S, Shekha M, Faris P, Guerra G. Endothelial Ca(2+) signaling, angiogenesis and vasculogenesis: just what it takes to make a blood vessel. Int J Mol Sci. 2019;20(16):3962.PubMedPubMedCentral
101.
Iba T, Levi M, Levy JH. Sepsis-induced coagulopathy and disseminated intravascular coagulation. Semin Thromb Hemost. 2020;46(1):89–95.PubMed
102.
Iba T, Connors JM, Nagaoka I, Levy JH. Recent advances in the research and management of sepsis-associated DIC. Int J Hematol. 2021;113(1):24–33.PubMedPubMedCentral
103.
104.
Yang X, Cheng X, Tang Y, Qiu X, Wang Y, Kang H, et al. Bacterial endotoxin activates the coagulation cascade through gasdermin D-dependent phosphatidylserine exposure. Immunity. 2019;51(6):983-96 e6.PubMed
105.
Jhang WK, Park SJ. Evaluation of sepsis-induced coagulopathy in critically Ill pediatric patients with septic shock. Thromb Haemost. 2021;121(4):457–63.PubMed
106.
Norooznezhad AH, Mansouri K. Endothelial cell dysfunction, coagulation, and angiogenesis in coronavirus disease 2019 (COVID-19). Microvasc Res. 2021;137:104188.PubMedPubMedCentral
107.
Thachil J. Managing sepsis-associated coagulopathy remains an enigma. J Thromb Haemost. 2019;17(10):1586–9.PubMed
108.
Levi M, Sivapalaratnam S. Disseminated intravascular coagulation: an update on pathogenesis and diagnosis. Expert Rev Hematol. 2018;11(8):663–72.PubMed
109.
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–16.PubMed
110.
Iba T, Umemura Y, Wada H, Levy JH. Roles of coagulation abnormalities and microthrombosis in sepsis: pathophysiology, diagnosis, and treatment. Arch Med Res. 2021;52(8):788–97.PubMed
111.
Iba T, Levy JH, Raj A, Warkentin TE. Advance in the management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Clin Med. 2019;8(5):728.PubMedPubMedCentral
112.
Mehic D, Colling M, Pabinger I, Gebhart J. Natural anticoagulants: a missing link in mild to moderate bleeding tendencies. Haemophilia. 2021;27(5):701–9.PubMedPubMedCentral
113.
Walborn A, Rondina M, Mosier M, Fareed J, Hoppensteadt D. Endothelial dysfunction is associated with mortality and severity of coagulopathy in patients with sepsis and disseminated intravascular coagulation. Clin Appl Thromb Hemost. 2019;25:1076029619852163.PubMedPubMedCentral
114.
Umemura Y, Yamakawa K, Ogura H, Yuhara H, Fujimi S. Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials. J Thromb Haemost. 2016;14(3):518–30.PubMed
115.
Yamakawa K, Umemura Y, Murao S, Hayakawa M, Fujimi S. Optimal timing and early intervention with anticoagulant therapy for sepsis-induced disseminated intravascular coagulation. Clin Appl Thromb Hemost. 2019;25:1076029619835055.PubMedPubMedCentral
116.
Giustozzi M, Ehrlinder H, Bongiovanni D, Borovac JA, Guerreiro RA, Gasecka A, et al. Coagulopathy and sepsis: pathophysiology, clinical manifestations and treatment. Blood Rev. 2021;50:100864.PubMed
117.
118.
Venet F, Rimmele T, Monneret G. Management of sepsis-induced immunosuppression. Crit Care Clin. 2018;34(1):97–106.PubMed
119.
Santos JC, Dick MS, Lagrange B, Degrandi D, Pfeffer K, Yamamoto M, et al. LPS targets host guanylate-binding proteins to the bacterial outer membrane for non-canonical inflammasome activation. EMBO J. 2018;37(6):e98089.PubMedPubMedCentral
120.
121.
Tani T, Shimizu T, Tani M, Shoji H, Endo Y. Anti-endotoxin properties of polymyxin B-immobilized fibers. Adv Exp Med Biol. 2019;1145:321–41.PubMedPubMedCentral
122.
Krishnan M, Choi J, Choi S, Kim Y. Anti-endotoxin 9-meric peptide with therapeutic potential for the treatment of endotoxemia. J Microbiol Biotechnol. 2021;31(1):25–32.PubMed
123.
Bruse N, Leijte GP, Pickkers P, Kox M. New frontiers in precision medicine for sepsis-induced immunoparalysis. Expert Rev Clin Immunol. 2019;15(3):251–63.PubMed
124.
Sang N, Jiang L, Wang Z, Zhu Y, Lin G, Li R, et al. Bacteria-targeting liposomes for enhanced delivery of cinnamaldehyde and infection management. Int J Pharm. 2022;612:121356.PubMed
125.
Zariri A, van der Ley P. Biosynthetically engineered lipopolysaccharide as vaccine adjuvant. Expert Rev Vaccines. 2015;14(6):861–76.PubMed
126.
Chiu TW, Peng CJ, Chen MC, Hsu MH, Liang YH, Chiu CH, et al. Constructing conjugate vaccine against salmonella typhimurium using lipid-A free lipopolysaccharide. J Biomed Sci. 2020;27(1):89.PubMedPubMedCentral
127.
Zhu H, Rollier CS, Pollard AJ. Recent advances in lipopolysaccharide-based glycoconjugate vaccines. Expert Rev Vaccines. 2021;20(12):1515–38.PubMed
128.
Correa W, Heinbockel L, Martinez-de-Tejada G, Sanchez S, Garidel P, Schurholz T, et al. Synthetic Anti-lipopolysaccharide peptides (SALPs) as effective inhibitors of pathogen-associated molecular patterns (PAMPs). Adv Exp Med Biol. 2019;1117:111–29.PubMed
129.
Heinbockel L, Weindl G, Martinez-de-Tejada G, Correa W, Sanchez-Gomez S, Barcena-Varela S, et al. Inhibition of lipopolysaccharide- and lipoprotein-induced inflammation by antitoxin peptide Pep19–2.5. Front Immunol. 2018;9:1704.PubMedPubMedCentral
130.
Yahaya MAF, Bakar ARA, Stanslas J, Nordin N, Zainol M, Mehat MZ. Insights from molecular docking and molecular dynamics on the potential of vitexin as an antagonist candidate against lipopolysaccharide (LPS) for microglial activation in neuroinflammation. BMC Biotechnol. 2021;21(1):38.PubMedPubMedCentral
131.
Li C, Wang J, Zhao M, Zhang S, Zhang Y. Toll-like receptor 4 antagonist FP7 alleviates lipopolysaccharide-induced septic shock via NF-kB signaling pathway. Chem Biol Drug Des. 2021;97(6):1151–7.PubMed
132.
Shi C, Wang X, Wang L, Meng Q, Guo D, Chen L, et al. A nanotrap improves survival in severe sepsis by attenuating hyperinflammation. Nat Commun. 2020;11(1):3384.PubMedPubMedCentral
133.
Peng Z, Zhang X, Yuan L, Li T, Chen Y, Tian H, et al. Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing. J Nanobiotechnol. 2021;19(1):383.
134.
Sun JD, Li Q, Haoyang WW, Zhang DW, Wang H, Zhou W, et al. Adsorption-based detoxification of endotoxins by porous flexible organic frameworks. Mol Pharm. 2022;19(3):953–62.PubMed
135.
Shin SH, Kim EK, Lee KY, Kim HS. TNF-alpha antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats. BMC Neurosci. 2019;20(1):45.PubMedPubMedCentral
136.
Muthumalage T, Rahman I. Cannabidiol differentially regulates basal and LPS-induced inflammatory responses in macrophages, lung epithelial cells, and fibroblasts. Toxicol Appl Pharmacol. 2019;382:114713.PubMedPubMedCentral
137.
Dai S, Ye B, Chen L, Hong G, Zhao G, Lu Z. Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation. Phytother Res PTR. 2021;35(9):5203–13.PubMed
138.
Wang L, Lei W, Zhang S, Yao L. MCC950, a NLRP3 inhibitor, ameliorates lipopolysaccharide-induced lung inflammation in mice. Bioorg Med Chem. 2021;30:115954.PubMed
139.
Ronco C, Ricci Z, Husain-Syed F. From multiple organ support therapy to extracorporeal organ support in critically Ill patients. Blood Purif. 2019;48(2):99–105.PubMed
140.
Vincent JL. Introduction to extracorporeal multiple organ support. Blood Purif. 2019;48(2):97–8.PubMed
141.
Zampieri FG, Mazza B. Mechanical ventilation in sepsis: a reappraisal. Shock. 2017;47(1S Suppl 1):41–6.PubMed
142.
Brechot N, Hajage D, Kimmoun A, Demiselle J, Agerstrand C, Montero S, et al. Venoarterial extracorporeal membrane oxygenation to rescue sepsis-induced cardiogenic shock: a retrospective, multicentre, international cohort study. Lancet. 2020;396(10250):545–52.PubMed
143.
King CS, Roy A, Ryan L, Singh R. Cardiac support: emphasis on venoarterial ECMO. Crit Care Clin. 2017;33(4):777–94.PubMed
144.
Ronco C, Chawla L, Husain-Syed F, Kellum JA. Rationale for sequential extracorporeal therapy (SET) in sepsis. Crit Care. 2023;27(1):50.PubMedPubMedCentral
145.
146.
Jamwal S, Sharma S. Vascular endothelium dysfunction: a conservative target in metabolic disorders. Inflamm Res. 2018;67(5):391–405.PubMed
147.
Feng J, Liu L, Yao F, Zhou D, He Y, Wang J. The protective effect of tanshinone IIa on endothelial cells: a generalist among clinical therapeutics. Expert Rev Clin Pharmacol. 2021;14(2):239–48.PubMed
148.
Yao RQ, Ren C, Xia ZF, Yao YM. Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles. Autophagy. 2021;17(2):385–401.PubMed
149.
Amersfoort J, Eelen G, Carmeliet P. Immunomodulation by endothelial cells—partnering up with the immune system? Nat Rev Immunol. 2022;22:576.PubMedPubMedCentral
150.
Duan H, Zhang Q, Liu J, Li R, Wang D, Peng W, et al. Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis. Pharmacol Res. 2021;168:105599.PubMed
151.
Sullivan RC, Rockstrom MD, Schmidt EP, Hippensteel JA. Endothelial glycocalyx degradation during sepsis: Causes and consequences. Matrix Biol Plus. 2021;12:100094.PubMedPubMedCentral
152.
153.
Qian Y, Wang Z, Lin H, Lei T, Zhou Z, Huang W, et al. TRIM47 is a novel endothelial activation factor that aggravates lipopolysaccharide-induced acute lung injury in mice via K63-linked ubiquitination of TRAF2. Signal Transduct Target Ther. 2022;7(1):148.PubMedPubMedCentral
154.
Vincent JL, Grimaldi D. Novel interventions: what’s new and the future. Crit Care Clin. 2018;34(1):161–73.PubMed
155.
McHale TM, Garciarena CD, Fagan RP, Smith SGJ, Martin-Loches I, Curley GF, et al. Inhibition of vascular endothelial cell leak following Escherichia coli attachment in an experimental model of sepsis. Crit Care Med. 2018;46(8):e805–10.PubMed
156.
Metadata
Title
Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis
Authors
Min Wang
Jun Feng
Daixing Zhou
Junshuai Wang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01301-5

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