دورية أكاديمية
Toll-like receptor expression and functional behavior in platelets from patients with systemic lupus erythematosus.
| العنوان: | Toll-like receptor expression and functional behavior in platelets from patients with systemic lupus erythematosus. |
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| المؤلفون: | Baroni Pietto MC; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina., Glembotsky AC; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina., Lev PR; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina., Marín Oyarzún CR; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina., De Luca G; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina., Gomez G; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Department of Rheumatology. Buenos Aires, Argentina., Collado MV; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Department of Rheumatology. Buenos Aires, Argentina., Charó N; National Scientific and Technical Research Council-National Academy of Medicine, Institute of Experimental Medicine, Laboratory of Experimental Thrombosis and Immunobiology of Inflammation. Buenos Aires, Argentina., Cellucci AS; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina., Heller PG; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina., Goette NP; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina., Marta RF; University of Buenos Aires, School of Medicine, Institute for Medical Research Alfredo Lanari. Buenos Aires, Argentina; National Scientific and Technical Research Council, University of Buenos Aires, Institute for Medical Research, Department of Hematology Research. Buenos Aires, Argentina. Electronic address: rfmarta@conicet.gov.ar. |
| المصدر: | Immunobiology [Immunobiology] 2024 Jan; Vol. 229 (1), pp. 152782. Date of Electronic Publication: 2023 Dec 28. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8002742 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3279 (Electronic) Linking ISSN: 01712985 NLM ISO Abbreviation: Immunobiology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2005->: Amsterdam : Elsevier Original Publication: Stuttgart ; New York, Fischer. |
| مواضيع طبية MeSH: | HMGB1 Protein*/metabolism , Lupus Erythematosus, Systemic*, Humans ; CD40 Ligand ; von Willebrand Factor/metabolism ; Toll-Like Receptors/metabolism ; Blood Platelets/metabolism ; Inflammation/metabolism ; Toll-Like Receptor 9 |
| مستخلص: | Background: Multiple blood cell abnormalities participate in the development of inflammation in systemic lupus erythematosus (SLE). Although platelets have been suggested as one of these contributors through the release of their content during activation, there are limited specific data about their role as immune players in SLE. Materials and Methods: Thirteen SLE patients were included. Flow cytometry was used to measure Toll-like receptors (TLR) 2, 4, and 9 in resting platelets, platelet-activation markers (PAC-1 binding, P-selectin, CD63, and CD40 ligand -L) and platelet-leukocyte aggregates before and after specific TLR stimulation. Soluble CD40L and von Willebrand factor (vWf) release from stimulated platelets was measured using ELISA. Results: In resting conditions, SLE platelets showed normal expression levels of TLR 2, 4 and 9. Platelet surface activation markers, soluble CD40L, and vWf release were normal at baseline and after TLR stimulation. Platelet-monocyte aggregates were elevated in resting conditions in SLE samples and showed only a marginal increase after TLR stimulation, while baseline and stimulated platelet-neutrophil and platelet-lymphocyte aggregates were normal. C-reactive protein levels positively correlated with platelet-monocyte aggregates both at baseline and after stimulation with the TLR-2 agonist PAM3CSK4, suggesting these complexes could reflect the inflammatory activity in SLE. In our cohort, 12 of 13 patients received treatment with hydroxychloroquine (HCQ), a known inhibitor of endosomal activity and a potential inhibitor of platelet activation. The fact that SLE platelets showed an adequate response to TLR agonists suggests that, despite this treatment, they retain the ability to respond to the increased levels of damage-associated molecular patterns (DAMPs), which represent known TLR ligands, present in the circulation of SLE patients. Interestingly, elevated plasma levels of high mobility group box 1 (HMGB1), a classical DAMP, correlated with vWf release from TLR-stimulated platelets, suggesting that HMGB1 may also be released by platelets, thereby creating a positive feedback loop for platelet activation that contributes to inflammation. Conclusion: Our study demonstrates normal platelet TLR expression and function together with increased circulating platelet-monocyte aggregates. In addition, a direct correlation was observed between plasma HMGB1 levels and platelet vWf release following TLR2 stimulation. This platelet behavior in a group of patients undergoing HCQ treatment suggests that platelets could play a role in the inflammatory state of SLE. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Platelets; Systemic lupus erythematosus; Toll-like receptors |
| المشرفين على المادة: | 0 (HMGB1 Protein) 147205-72-9 (CD40 Ligand) 0 (von Willebrand Factor) 0 (Toll-Like Receptors) 0 (Toll-Like Receptor 9) |
| تواريخ الأحداث: | Date Created: 20231230 Date Completed: 20240122 Latest Revision: 20240122 |
| رمز التحديث: | 20240122 |
| DOI: | 10.1016/j.imbio.2023.152782 |
| PMID: | 38159527 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1878-3279 |
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| DOI: | 10.1016/j.imbio.2023.152782 |