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. |
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| 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.) |
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| 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 |
Full Text Finder | تدمد: | 1540-0514 |
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| DOI: | 10.1097/SHK.0000000000002397 |