دورية أكاديمية
INHIBITION OF INTEGRIN VLA-3 AND TETRASPANIN CD151 PROTECTS AGAINST NEUTROPHIL-MEDIATED ENDOTHELIAL DAMAGE.
العنوان: | INHIBITION OF INTEGRIN VLA-3 AND TETRASPANIN CD151 PROTECTS AGAINST NEUTROPHIL-MEDIATED ENDOTHELIAL DAMAGE. |
---|---|
المؤلفون: | Ciambella C; Rhode Island Hospital, Department of Surgery, Division of Surgical Research, Alpert Medical School of Brown University, Providence, Rhode Island., Witt H, Dickinson CM; Rhode Island Hospital, Department of Surgery, Division of Surgical Research, Alpert Medical School of Brown University, Providence, Rhode Island., Smith ML; Rhode Island Hospital, Department of Surgery, Division of Surgical Research, Alpert Medical School of Brown University, Providence, Rhode Island., Coburn N; Rhode Island Hospital, Department of Surgery, Division of Surgical Research, Alpert Medical School of Brown University, Providence, Rhode Island., Messina N; Rhode Island Hospital, Department of Surgery, Division of Surgical Research, Alpert Medical School of Brown University, Providence, Rhode Island., Heffernan DS; Rhode Island Hospital, Department of Surgery, Division of Surgical Research, Alpert Medical School of Brown University, Providence, Rhode Island., Kim M; Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York., Reichner JS; Rhode Island Hospital, Department of Surgery, Division of Surgical Research, Alpert Medical School of Brown University, Providence, Rhode Island. |
المصدر: | Shock (Augusta, Ga.) [Shock] 2024 Aug 01; Vol. 62 (2), pp. 165-172. Date of Electronic Publication: 2024 May 23. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9421564 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-0514 (Electronic) Linking ISSN: 10732322 NLM ISO Abbreviation: Shock Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2002- : Philadelphia : Lippincott Williams & Wilkins Original Publication: Augusta, GA : BioMedical Press, [1994- |
مواضيع طبية MeSH: | Neutrophils*/metabolism , Tetraspanin 24*/metabolism , Sepsis*/metabolism , Integrin alpha3beta1*/metabolism, Humans ; Male ; Female ; Human Umbilical Vein Endothelial Cells/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Middle Aged ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism |
مستخلص: | Abstract: Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. However, in cases of sepsis, the interaction of endothelial cells with highly activated neutrophils can cause damage vascular damage. The identification of molecules that are essential for neutrophil diapedesis may reveal targets of therapeutic opportunity for preservation of endothelial function in the presence of critical illness. We tested the hypothesis that inhibition of neutrophil β1 integrin very late antigen-3 (VLA-3; α3β1) and/or inhibition of the tetraspanin (TM4) family member CD151 would protect against neutrophil-mediated loss of endothelial function. Methods: Blood was obtained from septic patients or healthy donors. Neutrophils were purified, and aliquots were treated with/without proinflammatory molecules. Confluent human umbilical vascular endothelial cells were activated with TNF-α. Electric cell impedance sensing was used to determine monolayer resistance over time after the addition of neutrophils that were treated with blocking antibodies against VLA-3 and/or CD151 or isotype controls. Groups (depending on relevancy) were analyzed by Mann-Whitney U test, Wilcoxon test, or repeated-measures one-way ANOVA. Results: Neutrophils from septic patients and neutrophils activated ex vivo reduced endothelial monolayer resistance to a greater extent than neutrophils from healthy donors. Antibody blockade of VLA-3 and/or CD151 significantly reduced activation-associated endothelial damage. Similar findings were demonstrated on fibronectin, collagen I, collagen IV, and laminin, suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. Conclusion: This report identifies VLA-3 and CD151 on the activated human neutrophil, which are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.) |
References: | Ley K, Hoffman HM, Kubes P, et al. Neutrophils: new insights and open questions. Sci Immunol . 2018;3(30):eaat4579. Wei Y, Kim J, Ernits H, et al. The septic neutrophil—friend or foe. Shock . 2021;55(2):147–155. Liew PX, Kubes P. The neutrophil's role during health and disease. Physiol Rev . 2019;99(2):1223–1248. Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood . 2003;101(10):3765–3777. Martin-Fernandez M, Vaquero-Roncero LM, Almansa R, et al. Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients. BJS Open . 2020;4(3):524–534. Brown KA, Brain SD, Pearson JD, et al. Neutrophils in development of multiple organ failure in sepsis. Lancet . 2006;368(9530):157–169. Crouser ED, Matthay MA. Endothelial damage during septic shock: significance and implications for future therapies. Chest . 2017;152(1):1–3. Lerman YV, Lim K, Hyun YM, et al. Sepsis lethality via exacerbated tissue infiltration and TLR-induced cytokine production by neutrophils is integrin alpha3beta1-dependent. Blood . 2014;124(24):3515–3523. Mitroulis I, Chavakis T. α3β1 is INTEGRAL to septic neutrophils. Blood . 2014;124(24):3507–3508. Samson GPB, Legler DF. Membrane compartmentalization and scaffold proteins in leukocyte migration. Front Cell Dev Biol . 2020;8:285. Yauch RL, Berditchevski F, Harler MB, et al. Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Mol Biol Cell . 1998;9(10):2751–2765. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA . 2016;315(8):801–810. Johnson CM, O'Brien XM, Byrd AS, et al. Integrin cross-talk regulates the human neutrophil response to fungal beta-glucan in the context of the extracellular matrix: a prominent role for VLA3 in the antifungal response. J Immunol . 2017;198(1):318–334. Esmann L, Idel C, Sarkar A, et al. Phagocytosis of apoptotic cells by neutrophil granulocytes: diminished proinflammatory neutrophil functions in the presence of apoptotic cells. J Immunol . 2010;184(1):391–400. Matlung HL, Babes L, Zhao XW, et al. Neutrophils kill antibody-opsonized cancer cells by trogoptosis. Cell Rep . 2018;23(13):3946–3959.e6. Witt H, Yan Z, Henann D, et al. Mechanosensitive traction force generation is regulated by the neutrophil activation state. Sci Rep . 2023;13(1):11098. Dickinson CM, LeBlanc BW, Edhi MM, et al. Leukadherin-1 ameliorates endothelial barrier damage mediated by neutrophils from critically ill patients. J Intensive Care . 2018;6:19. Fox ED, Heffernan DS, Cioffi WG, et al. Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity. Crit Care . 2013;17(5):R226. Tsikitis VL, Morin NA, Harrington EO, et al. The lectin-like domain of complement receptor 3 protects endothelial barrier function from activated neutrophils. J Immunol . 2004;173(2):1284–1291. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol . 2013;13(3):159–175. Lamers C, Pluss CJ, Ricklin D. The promiscuous profile of complement receptor 3 in ligand binding, immune modulation, and pathophysiology. Front Immunol . 2021;12:662164. Diamond MS, Staunton DE, de Fougerolles AR, et al. ICAM-1 (CD54): a counter-receptor for mac-1 (CD11b/CD18). J Cell Biol . 1990;111(6 Pt 2):3129–3139. Diamond MS, Staunton DE, Marlin SD, et al. Binding of the integrin mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell . 1991;65(6):961–971. |
معلومات مُعتمدة: | R01 HL147525 United States HL NHLBI NIH HHS |
المشرفين على المادة: | 0 (Tetraspanin 24) 0 (Integrin alpha3beta1) 0 (CD151 protein, human) 0 (Tumor Necrosis Factor-alpha) |
تواريخ الأحداث: | Date Created: 20240530 Date Completed: 20240717 Latest Revision: 20240815 |
رمز التحديث: | 20240815 |
مُعرف محوري في PubMed: | PMC11254560 |
DOI: | 10.1097/SHK.0000000000002397 |
PMID: | 38813923 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1540-0514 |
---|---|
DOI: | 10.1097/SHK.0000000000002397 |