Alteration of Spleen Macrophage Phenotypes Impacts Exosomes-Related Proteins in Gentamicin Toxicity Model

Sarah Ali Abdelhameed, Basma Emad Aboulhoda, Nivin Sharawy, Mohamed Mansour Khalifa, Hend Abdallah, Laila Rashed, Omaima Mohammed Abdelwahed

Article ID: 7930
Vol 38, Issue 3, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243803.198
Received: 20 March 2024; Accepted: 20 March 2024; Available online: 20 March 2024; Issue release: 20 March 2024

Abstract

Background: Necroinflammation loop is a pathologic hallmark of organ dysfunction. That is owed to a distorted balance between the pro-inflammatory (M1) and the anti-inflammatory (M2) macrophages. We aimed to explore whether low-intensity pulsed ultrasound (LIPUS) and/or splenectomy could ameliorate necroinflammation by increasing M2 macrophages and modulating the exosomes-related proteins. Method: Rats were allocated into 2 groups: Sham and splenectomy (Splen). After that, rats were divided into LIPUS untreated and treated subgroups. Rats in each subgroup were subjected to either vehicle (sham, sham + LIPUS) or gentamicin (GM) (GM, GM + LIPUS, Splen + GM, Splen + GM + LIPUS). Biochemical and immunohistological analyses assessed macrophage polarization, necroptosis, exosomes-related markers, and exosomes-related proteins. Results: We found that LIPUS successfully reversed the effects of GM, LIPUS significantly-decreased (p < 0.05) necroinflammation markers through significant downshifting (p < 0.05) of M1 macrophage polarization, and noticeable modification (p < 0.05) of the exosome-related proteins (Milk fat globule-EGF factor 8 (MFG-E8), heat shock protein 70 (Hsp70)). Conclusion: Spleen could be a promising target for LIPUS via restoring M1/M2 balance and modulation of exosomes-related proteins.


Keywords

Notch 4;exosomes;macrophages;MFG-E8;Hsp70


References

Supporting Agencies



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