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Tobacco Smoke and E‐Vapor Initiate Kupffer Cell Inflammatory Responses

Cardiovascular risk factors instigate cardiovascular diseases through numerous mechanisms. Recently, we have shown that ingested cardiovascular risk factors can initiate Kupffer cell innate immune responses, leading to platelet and endothelial cell inflammatory/thrombotic reactions. Here, we aimed to investigate the role of tobacco smoke, a well‐known risk factor, and e‐vapor, a source of fine particulate matter and oxidative stressors, on Kupffer cell activities. We hypothesized that the exposure of Kupffer cells to tobacco smoke or e‐vapor would initiate innate immune responses. Immortalized Kupffer cells were cultured and exposed to mainstream or sidestream tobacco smoke extracts or e‐vapor extracts prepared from different nicotine containing e‐juice formulations. Kupffer cell complement deposition, complement receptor activation, cytokine release and viability was quantified as a function of extract exposure. Platelets were subjected to Kupffer cell conditioned media, to determine the indirect activation of platelets by Kupffer cells. We observed a significant increase in Kupffer cell innate inflammatory responses after exposure to physiologically relevant concentrations of tobacco smoke extracts or e‐vapor. As nicotine concentration in e‐juice increased, the activity of Kupffer cells also increased. Kupffer cell viability was reduced after exposure to tobacco or e‐vapor extracts. Platelets exposed to Kupffer cell conditioned media also showed an increased aggregation potential towards a thrombin receptor antagonist. Platelet activities were at least partially mediated by an enhanced expression of GPIIb/IIIa. Thus, these data suggests that Kupffer cells are responsive to non‐ingested cardiovascular risk factors and that these signals can be indirectly passed to platelets.