Selective Activation of Human Monocytes Exposed Ex Vivo to Different E-Cigarette Aerosols: Possible Role in Subclinical Inflammation

Electronic cigarettes (ECs) are promoted as a safer alternative to traditional cigarettes, yet their impact on immune cells remains incompletely understood. This study investigates the activation of human primary adherent and non-adherent monocytes exposed ex vivo to aerosols from four flavored ECs (classic tobacco, menthol, watermelon, and strawberry) compared to cigarette smoke (CS) and nicotine alone. EC aerosols (ECEs) induced modest cytotoxicity, oxidative stress, and superoxide dismutase activity compared to CS, with high cell response heterogeneity indicating subpopulation-specific effects. Adherent monocytes showed elevated integrin expression (CD11a, CD11b), ICAM-1 (CD54), TNFα, and oxidative stress versus non-adherent cells, amplified by ECE. Dual fluorescence flow cytometry (green DCF for ROS and red for anti-TNFα Ab) revealed shifts toward pro-inflammatory/oxidative quadrants, particularly upper-right high-intensity relatively small subsets with macrophage M1-like CD68 expression in adherent cells. ECEs reduced phagocytosis in adherent monocytes, mimicking CS effects, probably driven by non-nicotine components. Strawberry flavor (ECE 4) elicited the strongest TNFα induction. These findings demonstrate EC-induced subclinical inflammation via selective monocyte activation, potentially contributing to chronic cardiopulmonary risks despite significantly lower overall toxicity than CS.