دورية أكاديمية
Platelet-derived β2M regulates monocyte inflammatory responses.
| العنوان: | Platelet-derived β2M regulates monocyte inflammatory responses. |
|---|---|
| المؤلفون: | Hilt ZT; Aab Cardiovascular Research Institute., Pariser DN; Aab Cardiovascular Research Institute., Ture SK; Aab Cardiovascular Research Institute., Mohan A; Aab Cardiovascular Research Institute., Quijada P; Aab Cardiovascular Research Institute., Asante AA; Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York, USA., Cameron SJ; Aab Cardiovascular Research Institute., Sterling JA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.; Department of Cancer Biology, Medicine, Division of Clinical Pharmacology, Bone Biology Center, and Biomedical Engineering, and.; Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA., Merkel AR; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.; Department of Cancer Biology, Medicine, Division of Clinical Pharmacology, Bone Biology Center, and Biomedical Engineering, and.; Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA., Johanson AL; Aab Cardiovascular Research Institute., Jenkins JL; Department of Biochemistry and., Small EM; Aab Cardiovascular Research Institute., McGrath KE; Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York, USA., Palis J; Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York, USA., Elliott MR; Department of Microbiology and Immunology, University of Rochester School of Medicine, Rochester, New York, USA., Morrell CN; Aab Cardiovascular Research Institute.; Department of Microbiology and Immunology, University of Rochester School of Medicine, Rochester, New York, USA. |
| المصدر: | JCI insight [JCI Insight] 2019 Mar 07; Vol. 4 (5). Date of Electronic Publication: 2019 Mar 07 (Print Publication: 2019). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: eCollection Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Blood Platelets/*metabolism , Monocytes/*metabolism , beta 2-Microglobulin/*metabolism, Animals ; Cell Differentiation ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Chaperones ; Platelet Activation ; Receptor, Transforming Growth Factor-beta Type II/genetics ; Receptors, Transforming Growth Factor beta/genetics ; Receptors, Transforming Growth Factor beta/metabolism ; Signal Transduction ; THP-1 Cells ; beta 2-Microglobulin/genetics |
| مستخلص: | β-2 Microglobulin (β2M) is a molecular chaperone for the major histocompatibility class I (MHC I) complex, hemochromatosis factor protein (HFE), and the neonatal Fc receptor (FcRn), but β2M may also have less understood chaperone-independent functions. Elevated plasma β2M has a direct role in neurocognitive decline and is a risk factor for adverse cardiovascular events. β2M mRNA is present in platelets at very high levels, and β2M is part of the activated platelet releasate. In addition to their more well-studied thrombotic functions, platelets are important immune regulatory cells that release inflammatory molecules and contribute to leukocyte trafficking, activation, and differentiation. We have now found that platelet-derived β2M is a mediator of monocyte proinflammatory differentiation through noncanonical TGFβ receptor signaling. Circulating monocytes from mice lacking β2M only in platelets (Plt-β2M-/-) had a more proreparative monocyte phenotype, in part dependent on increased platelet-derived TGFβ signaling in the absence of β2M. Using a mouse myocardial infarction (MI) model, Plt-β2M-/- mice had limited post-MI proinflammatory monocyte responses and, instead, demonstrated early proreparative monocyte differentiation, profibrotic myofibroblast responses, and a rapid decline in heart function compared with WT mice. These data demonstrate a potentially novel chaperone-independent, monocyte phenotype-regulatory function for platelet β2M and that platelet-derived 2M and TGFβ have opposing roles in monocyte differentiation that may be important in tissue injury responses. |
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| معلومات مُعتمدة: | R01 DK098251 United States DK NIDDK NIH HHS; T32 AI049815 United States AI NIAID NIH HHS; UL1 TR002001 United States TR NCATS NIH HHS; UL1 TR000042 United States TR NCATS NIH HHS; K08 HL128856 United States HL NHLBI NIH HHS; 18PRE34030161 United States AHA American Heart Association-American Stroke Association; P30 AI078498 United States AI NIAID NIH HHS; T32 AI007285 United States AI NIAID NIH HHS; R01 HL141106 United States HL NHLBI NIH HHS; R01 HL124018 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: Platelets; Vascular Biology |
| المشرفين على المادة: | 0 (Molecular Chaperones) 0 (Receptors, Transforming Growth Factor beta) 0 (beta 2-Microglobulin) EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II) |
| تواريخ الأحداث: | Date Created: 20190201 Date Completed: 20200601 Latest Revision: 20240413 |
| رمز التحديث: | 20240413 |
| مُعرف محوري في PubMed: | PMC6483513 |
| DOI: | 10.1172/jci.insight.122943 |
| PMID: | 30702442 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2379-3708 |
|---|---|
| DOI: | 10.1172/jci.insight.122943 |