Mechanosensitivity of macrophage polarization: comparing small molecule leukadherin-1 to substrate stiffness

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 6, 2025

Macrophages sustain tissue homeostasis through host defense and wound repair. To promote defense, macrophages upregulate surface markers associated with antigen processing secrete pro-inflammatory mediators such as IL-6 IL-1β. After pathogen clearance, shift phenotype to Shifts in phenotypes are termed "polarization" have historically been modeled by exposure soluble LPS+IFNγ (host defense) or IL-4+IL-13 (tissue repair). Greater emphasis is now being placed on understanding how the mechanical environment of macrophages, compliance, regulates responses. Here, we compare incubation primary collagen-coated silica gels varying stiffness treatment small molecule integrin activator, leukadherin-1 (LA1), examine substrate alters macrophage polarization response multiple stimuli. LA1 was developed an immunomodulator treat inflammatory diseases impairing trafficking cells. A recent clinical trial examining solid tumors terminated early because no benefit observed. We hypothesized that may exert additional, unexpected effects replicating mechanotransduction. Specifically, would mimic stiffer substrates, both conditions be predicted activate integrins. Our results show soft (0.2 kPa) trends towards upregulation molecules, contrast prior reports using different experimental systems. further substrates enhance NLRP3-mediated IL-1β production, compared stiff, mouse human macrophages. mimicked stiff inhibiting NLRP3 activation regulating expression several but differed reducing production. responses regulated adhesion-based, integrin-mediated signaling. Modulation production supports possibility repurposing NLRP3-dependent diseases.

Language: Английский

Superhydrophobicity Effects on Spheroid Formation and Polarization of Macrophages

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(8), P. 1042 - 1042

Published: Aug. 7, 2024

The interaction of biomaterials with the immune system is ruled by action macrophages. surface features these biomaterials, like wettability, which an expression chemical composition, texture, and geometry, can affect macrophages response. Such parameters be then efficiently exploited to improve biocompatibility lowering undesired immunological reactions at same time creating substrate for positive interactions. In this work, preparation physicochemical characterization highly water-repellent surfaces develop characterize 3D spheroids derived from monocyte-macrophages (RAW 264.7 cell line) has been carried out. As a measure viability over time, obtained aggregates have transferred under standard 2D culture conditions. Significant changes on morphology-associated polarization cellular entities evaluated nanoscale through profilometry. results suggested that spheroid formation using repellent substrates induced activation M2-type cells. This simple cost-effective approach used preparing M2-based regenerative purposes.

Language: Английский