دورية أكاديمية
Platelet-derived β2m regulates age related monocyte/macrophage functions.
| العنوان: | Platelet-derived β2m regulates age related monocyte/macrophage functions. |
|---|---|
| المؤلفون: | Hilt ZT; Aab Cardiovascular Research Institute, University of Rochester School of Medicine, Box CVRI, Rochester, NY 14652, USA., Ture SK; Aab Cardiovascular Research Institute, University of Rochester School of Medicine, Box CVRI, Rochester, NY 14652, USA., Mohan A; Aab Cardiovascular Research Institute, University of Rochester School of Medicine, Box CVRI, Rochester, NY 14652, USA., Arne A; Aab Cardiovascular Research Institute, University of Rochester School of Medicine, Box CVRI, Rochester, NY 14652, USA., Morrell CN; Aab Cardiovascular Research Institute, University of Rochester School of Medicine, Box CVRI, Rochester, NY 14652, USA.; Department of Microbiology and Immunology, University of Rochester School of Medicine, Rochester, NY 14652, USA. |
| المصدر: | Aging [Aging (Albany NY)] 2019 Dec 18; Vol. 11 (24), pp. 11955-11974. Date of Electronic Publication: 2019 Dec 18. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, NY : Impact Journals, LLC |
| مواضيع طبية MeSH: | Aging/*immunology , Aging/*metabolism , Blood Platelets/*metabolism , Macrophages/*metabolism , beta 2-Microglobulin/*metabolism, Aging/pathology ; Animals ; Blood Platelets/immunology ; Fibrosis/immunology ; Fibrosis/pathology ; Macrophages/immunology ; Mice ; Mice, Knockout ; Monocytes/immunology ; Monocytes/metabolism ; Myocardium/pathology ; Phenotype |
| مستخلص: | Platelets have central roles in both immune responses and development. Stimulated platelets express leukocyte adhesion molecules and release numerous immune modulatory factors that recruit and activate leukocytes, both at the sites of activation and distantly. Monocytes are innate immune cells with dynamic immune modulatory functions that change during the aging process, a phenomenon termed "inflammaging". We have previously shown that platelets are a major source of plasma beta-2 microglobulin (β2M) and that β2M induced a monocyte pro-inflammatory phenotype. Plasma β2M increases with age and is a pro-aging factor. We hypothesized that platelet derived β2M regulates monocyte phenotypes in the context of aging. Using wild-type (WT) and platelet specific β2M knockout mice (Plt-β2M -/- ) mice, we found that plasma β2M increased with age and correlated with increased circulating Ly6C Hi monocytes. However, aged Plt-β2M -/- mice had significantly fewer Ly6C Hi monocytes compared to WT mice. Quantitative real-time PCR of circulating monocytes showed that WT mouse monocytes were more "pro-inflammatory" with age, while Plt-β2M -/- derived monocytes adopted a "pro-reparative" phenotype. Older Plt-β2M -/- mice had a significant decline in heart function compared to age matched WT mice, as well as increased cardiac fibrosis and pro-fibrotic markers. These data suggest that platelet-derived β2M regulates age associated monocyte polarization, and a loss of platelet derived β2M shifted monocytes and macrophages to a pro-reparative phenotype and increased pro-fibrotic cardiac responses. Platelet regulation of monocyte phenotypes via β2M may maintain a balance between inflammatory and reparative signals that affects age related physiologic outcomes. |
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| معلومات مُعتمدة: | F31 HL145922 United States HL NHLBI NIH HHS; R01 HL141106 United States HL NHLBI NIH HHS; R01 HL142152 United States HL NHLBI NIH HHS; UL1 TR002001 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: aging; heart; inflammation; monocytes; platelets |
| المشرفين على المادة: | 0 (beta 2-Microglobulin) |
| تواريخ الأحداث: | Date Created: 20191220 Date Completed: 20201021 Latest Revision: 20201113 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6949047 |
| DOI: | 10.18632/aging.102520 |
| PMID: | 31852838 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-4589 |
|---|---|
| DOI: | 10.18632/aging.102520 |