基于生物介质中的刺激，巨噬细胞可以通过经典激活转化为M1促炎（抗癌）表型或另类激活的M2抗炎表型。无药物生物材料已经成为调节巨噬细胞表型的新治疗策略。其中，多糖通过它们与表面受体的结合来极化巨噬细胞为M1或M2表型。芸查聚糖（Levan）是一种水果聚糖，虽然与巨噬细胞的相互作用被很少探索，但已被提出作为一种新型生物材料。在本研究中，我们在体外研究了非水解和水解花盘单胞杆菌（Halomonas）芸查聚糖及其硫酸化衍生物与人巨噬细胞的相互作用。细胞存活研究表明，这些芸查聚糖与细胞兼容。此外，RNA测序分析显示，炎症相关途径被上调。这些结果与实时荧光定量聚合酶链反应相一致，显示在芸查聚糖处理后C-X-C模体化学因子配体8和白细胞介素6基因的表达水平更高，并使这些细胞发生从M2到M1的重编程。最后，细胞因子释放研究证实，水解芸查聚糖增加了促炎因子的分泌，并将IL-4偏架的巨噬细胞重编程为M1状态。总体实验结果表明，芸查聚糖能够引发经典巨噬细胞的激活，为其在需要促炎表型的治疗干预中的应用铺平了道路。Copyright © 2023 Elsevier Ltd. All rights reserved.

Based on stimuli in the biological milieu, macrophages can undergo classical activation into the M1 pro-inflammatory (anti-cancer) phenotype or to the alternatively activated M2 anti-inflammatory one. Drug-free biomaterials have emerged as a new therapeutic strategy to modulate macrophage phenotype. Among them, polysaccharides polarize macrophages to M1 or M2 phenotypes based on the surface receptors they bind. Levan, a fructan, has been proposed as a novel biomaterial though its interaction with macrophages has been scarcely explored. In this study, we investigate the interaction of non-hydrolyzed and hydrolyzed Halomonas levan and its sulfated derivative with human macrophages in vitro. Viability studies show that these levans are cell compatible. In addition, RNA-sequencing analysis reveals the upregulation of pro-inflammatory pathways. These results are in good agreement with real time-quantitative polymerase chain reaction that indicates higher expression levels of C-X-C Motif Chemokine Ligand 8 and interleukin-6 genes and the M2-to-M1 reprogramming of these cells upon levan treatment. Finally, cytokine release studies confirm that hydrolyzed levans increase the secretion of pro-inflammatory cytokines and reprogram IL-4-polarized macrophages to the M1 state. Overall findings indicate that Halomonas levans trigger a classical macrophage activation and pave the way for their application in therapeutic interventions requiring a pro-inflammatory phenotype.Copyright © 2023 Elsevier Ltd. All rights reserved.