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The percentage of FITC-positive THP-1 cells after the phagocytosis of FITC-labeled E. coli. THP-1(unst)—intact THP-1 cells; THP-1(control)—THP-1 cells stained with tripan blue (TB) and propidium iodide (PI); THP-1(E. coli)—THP-1 cells stained with TB and PI after incubation with FITC-labeled E. coli; +TNFα—THP-1 cells pre-incubated with TNFα; +LEVs(int)—THP-1 cells pre-incubated with LEVs(int); and +LEVs(TNFα)—THP-1 cells pre-incubated with LEVs(TNFα). Significant differences: *—p < 0.05; **—p < 0.01; and ***—p < 0.001.
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Communication between natural killer cells (NK cells) and monocytes/macrophages may play an important role in immunomodulation and regulation of inflammatory processes. The aim of this research was to investigate the impact of NK cell-derived large extracellular vesicles on monocyte function because this field is understudied. We studied how NK-cel...
Citations
... Previous studies have shown that LEVs, ranging from 1 to 10 µm, contain proteins and small RNAs, highlighting their potential for development as biomarkers in cancer [23]. LEVs produced by a natural killer cell line in vitro regulated the surface marker expression and function of monocyte/macrophage cell lines [24]. Moreover, some LEVs contain, transport, and release SEVs [25]. ...
Certain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) progression. We analyzed the mass spectrometry-based proteomic data of plasma EVs and synovial fluid (SF) EVs from knee OA patients (n = 16, 50% female). The identified surface markers of interest were further evaluated in plasma EVs from an independent cohort of knee OA patients (n = 30, 47% female) using flow cytometry. A total of 199 peptides with significant correlation between plasma and SF EVs were identified. Of these, 41.7% were linked to immune system processes, 15.5% to inflammatory responses, and 16.7% to the complement system. Crucially, five previously identified knee rOA severity-indicating surface markers—FGA, FGB, FGG, TLN1, and AMBP—were confirmed on plasma EV subpopulations in an independent cohort. These markers’ baseline frequencies on large plasma EVs predicted rOA progression with an AUC of 0.655–0.711. Notably, TLN1 was expressed in OA joint tissue, whereas FGA, FGB, FGG, and AMBP were predominantly liver derived. These surface markers define specific pathogenic EV subpopulations, offering potential OA prognostic biomarkers and novel therapeutic targets for disease modification.
Cell-to-cell communication plays a crucial role in many processes, both in physiological and pathological assets [...].
Extracellular vesicles (EVs) play crucial roles in aging. In this National Institutes on Aging-funded study, we sought to identify circulating extracellular vesicle (EV) biomarkers indicative of longevity. The plasma EV proteome of 48 older adults (mean age 77.2 ± 1.7 years [range 72–80]; 50% female, 50% Black, 50% < 2-year survival, 50% ≥ 10-year survival) was analyzed by high-resolution mass spectrometry and flow cytometry. The ability of EV peptides to predict longevity was evaluated in discovery ( n = 32) and validation ( n = 16) datasets with areas under receiver operating characteristic curves (AUCs). Longevity-associated large EV (LEV) plasma subpopulations were mainly related to immune cells (HLA-ABC ⁺ , CD9 ⁺ , and CD31 ⁺ ) and muscle cells (MCAD ⁺ and RyR2 ⁺ ). Of 7960 identified plasma EV peptides (519 proteins), 46.4% were related to the immune system and 10.1% to muscle. Compared with short-lived older adults, 756 EV peptides (131 proteins) had a higher abundance, and 130 EV peptides (78 proteins) had a lower abundance in long-lived adults. Among longevity-associated peptides, 437 (58 proteins) were immune system related, and 12 (2 proteins) were muscle related. Using just three to five plasma EV peptides (mainly complement components C2-C6), we achieved high predictive accuracy for longevity (AUC range 0.91–1 in a hold-out validation dataset). Our findings suggest that immune cells produce longevity-associated plasma EVs and elucidate fundamental mechanisms regulating aging and longevity. EV longevity predictors suggest there may be merit in targeting complement pathways to extend lifespan, for instance, with any one of the multiple complement inhibitors currently available or in clinical development.
