Monocytes treated with ciprofloxacin and oxyLDL express myristate, priming atherosclerosis

Area of Science:

• Cell Biology
• Immunology
• Pharmacology

Background:

• Antibiotics are crucial for treating severe infections but their misuse can lead to adverse effects.
• Oxidized low-density lipoprotein (oxyLDL) is implicated in the pathogenesis of atherosclerosis.
• Macrophage polarization plays a critical role in inflammatory processes, including atherosclerosis.

Purpose of the Study:

• To investigate the effects of ciprofloxacin on monocyte differentiation and foam cell formation.
• To explore the inflammatory profile of monocytes exposed to ciprofloxacin and oxyLDL.
• To identify molecular mechanisms linking ciprofloxacin exposure to atherosclerosis development.

Main Methods:

• Cell culture and morphological analysis of ciprofloxacin-treated monocytes.
• Oil Red O staining to detect lipid accumulation (foam cells).
• Flow cytometry for macrophage marker expression (CD64, CD23).
• Chemokine antibody array for inflammatory cytokine profiling.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic analysis.

Main Results:

• Ciprofloxacin induced significant morphological changes in monocytes, progressing to plaque-like and foam cells within 14 days.
• Ciprofloxacin-treated monocytes exhibited a proinflammatory macrophage phenotype (high CD64, low CD23) and secreted numerous proatherogenic chemokines.
• Myristic acid was found incorporated into a 68 kDa protein in ciprofloxacin-exposed, oxyLDL-treated monocytes, suggesting a role in foam cell formation and in vitro plaque development.

Conclusions:

• Ciprofloxacin exposure promotes monocyte-to-foam cell transition and induces a proinflammatory state, contributing to atherosclerosis.
• Myristic acid incorporation into proteins is a potential mechanism linking ciprofloxacin to atherosclerosis.
• Judicious use of ciprofloxacin, particularly in high-risk populations, is recommended to mitigate atherosclerosis risk.