HDL-Enriched Serum Promotes Granuloma Healing by Inducing M2 Macrophage Polarization

Abstract

Chronic inflammatory skin diseases represent a serious medical problem. However, the mechanisms underlying the transition from acute inflammation to resolution in cases of deep tissue damage are still not intirely unrevealed. Dynamic macrophage polarization plays a key role in healing processes, yet the therapeutic potential of metabolic regulators, such as high-density lipoproteins (HDL), in the context of CFA-induced granuloma are barely mentioned. This study investigates the ability of serum enriched with HDL (ABS) to modulate the immune response and accelerate tissue regeneration.

Our study hypothesizes that HDLs act as mediators in switching macrophages from the pro-inflammatory M1 phenotype to the reparative M2 phenotype. To test this hypothesis, we used an in vivo model: mice were administered a subcutaneous dose of CFA, thereby inducing a cutaneous granuloma. The efficacy of the therapy was assessed by systemic administration of ABS. The main research methods included flow cytometry for analyzing myeloid cell populations, quantitative RT-PCR for assessing the expression of pro- and anti-inflammatory markers (Nos2, Tnf, Arg1), and histopathological analysis with CD11b, F4/80, and CD206 antibodies for highlighting tissue damage dynamics. Our data indicate that HDL acts as a metabolic trigger that contributes to changes in the course of acute inflammation and leads to an increase in M2 macrophages at earlier stages. Histological analysis confirmed that the ratio of M1 to M2 macrophages shifts toward M2 macrophages due to the use of HDL-enriched serum. RT-PCR showed that the results of the group treated with HDL-enriched serum differed significantly in terms of the expression of Nos2, Tnf, and Arg1. Flow cytometry revealed a positive trend in skin sample healing based on the number of M2 macrophages. It can be concluded that HDL-enriched serum is an effective regulator of the inflammatory response, stimulating the transition to the resolution phase. Targeted intervention in the metabolic reprogramming of macrophages holds great potential for the development of new treatment strategies for severe and chronic skin pathologies.