Factors Released by Polarized Neutrophil-like Cells Modulate Cardiac Fibroblast Phenotype and Limit the Inflammatory...

Area of Science:

• Cardiology
• Immunology
• Cell Biology

Background:

• Cardiac fibroblasts (CFs) adopt specific phenotypes for scar formation post-myocardial infarction (MI).
• Neutrophils are key in post-MI healing, but their role in modulating CF phenotype is unclear.
• This study examines how mediators from pro-inflammatory (N1) and anti-inflammatory (N2) neutrophils affect CFs.

Purpose of the Study:

• To investigate the impact of neutrophil-derived soluble mediators on cardiac fibroblast (CF) phenotype.
• To understand how N1 and N2 neutrophil subtypes influence cardiac healing post-myocardial infarction (MI).

Main Methods:

• In vitro: Human CFs co-cultured with N1 or N2 neutrophil-like cells in a Transwell system.
• In vivo: Mouse neutrophils polarized to N1 or N2, with their soluble mediators (SN1/SN2) injected into infarcted myocardium post-MI.
• Analysis of inflammatory, remodeling, and pro-fibrotic markers in fibroblasts and tissue at 1 and 7 days post-MI.

Main Results:

• In vitro, N1 mediators induced a pro-inflammatory, matrix-degrading CF phenotype (IL-1β, IL-6, MCP-1, MMP-3/MMP-9).
• In vivo, both SN1 and SN2 treatments reduced pro-inflammatory markers (IL-1β, IL-6) at day 1 post-MI.
• At day 7 post-MI, SN1/SN2 treatments limited inflammation and mitigated fibrosis (reduced CCN2, α-SMA, ECM proteins).

Conclusions:

• N1 mediators promote a pro-inflammatory CF phenotype in vitro.
• Mediators from both N1 and N2 neutrophils support a balanced in vivo reparative response post-MI.
• Neutrophil mediators may mitigate adverse cardiac remodeling by limiting inflammation and fibrosis.