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Platelet-derived ?2m regulates age related monocyte/macrophage functions.

ABSTRACT: 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 (?2M) and that ?2M induced a monocyte pro-inflammatory phenotype. Plasma ?2M increases with age and is a pro-aging factor. We hypothesized that platelet derived ?2M regulates monocyte phenotypes in the context of aging. Using wild-type (WT) and platelet specific ?2M knockout mice (Plt-?2M^-/-) mice, we found that plasma ?2M increased with age and correlated with increased circulating Ly6C^Hi monocytes. However, aged Plt-?2M^-/- 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-?2M^-/- derived monocytes adopted a "pro-reparative" phenotype. Older Plt-?2M^-/- 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 ?2M regulates age associated monocyte polarization, and a loss of platelet derived ?2M shifted monocytes and macrophages to a pro-reparative phenotype and increased pro-fibrotic cardiac responses. Platelet regulation of monocyte phenotypes via ?2M may maintain a balance between inflammatory and reparative signals that affects age related physiologic outcomes.

SUBMITTER: Hilt ZT

PROVIDER: S-EPMC6949047 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Platelet-derived β2m regulates age related monocyte/macrophage functions.

Hilt Zachary T ZT Ture Sara K SK Mohan Amy A Arne Allison A Morrell Craig N CN

Aging 20191218 24

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 ...[more]

PMID: 31852838

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Platelet-derived ?2m regulates age related monocyte/macrophage functions.

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Platelet-derived β2m regulates age related monocyte/macrophage functions.

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