Monocytes treated with ciprofloxacin and oxyLDL express myristate, priming atherosclerosis.

Abstract

Antibiotics are essential in many life-threatening diseases. On the other hand, improper use of antibiotics can be disastrous. Cell morphological changes were observed in the ciprofloxacin-treated cells starting at 48 hours. Changes in cell morphology were continuously observed up to 14 days, which showed gradual morphological changes from monocyte to plaque-like cells at day 12, and foam cell, which is an intermediate stage in atherosclerosis was observed at day 8, which was confirmed with Oil Red O staining. Flow cytometry data revealed that oxidized LDL (oxyLDL)-induced cells showed 60.16% of CD64 (proinflammatory macrophage markers) and no expression of CD23 (anti-inflammatory macrophage markers), whereas ciprofloxacin-treated cells expressed 67.97% of CD64 and 13.78% of CD23. Chemokine antibody array analysis revealed that ciprofloxacin exposed cells showed a proinflammatory role (ENA78, Eotaxin1, Eotaxin2, IP-10, MIG, MIP-3β, SDF-1β, TECK, CXCL16, and Fractalkine). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) revealed that myristic acid was incorporated into a protein with 68 kDa molecular mass in exposing oxyLDL-induced monocytes with ciprofloxacin, which could be a reason for the observed foam cells and in vitro plaque formation. As myristic acid primes atherosclerosis, it is better to limit the intake of antibiotics like ciprofloxacin for common illness, specifically the high-risk patients, which may contribute to atherosclerosis.