Abstract
Histamine plays an important role in both normal physiology and various pathophysiological conditions. It upregulates the expression of inflammatory cytokines, including TNF-?, and endothelial cell adhesion molecules such as P-selectin and integrin ligands. These factors may trigger monocyte adhesion to arterial endothelium and subsequent accumulation of monocytes/macrophages in the arterial intima, leading to development of an atherosclerotic plaque. In this work, we target to investigate the effect of histamine on interactions of THP-1 (human acute monocytic leukemia cell line) with HUVEC monolayer in vitro. This analysis is conducted under flow conditions using the Bioflux 200 microfluidic shear flow system. According to our data, activation of HUVEC with histamine increases the rolling flux and decreases the rolling velocity of THP-1. Flow cytometric analysis indicates that P-selectin is the primary cell adhesion molecule involved in histamine-induced monocyte rolling. The histamine effect on cell rolling becomes more pronounced when it is used in combination with TNF-?. Histamine+TNF-? also lead to a significant increase in the number of firmly adherent monocytes. Parallel studies with OxLDL-stimulated endothelium show a less effect of OxLDL on monocyte rolling and adhesion than that of histamine+TNF-?. Overall, this study suggests that histamine may be an important regulator of atherogenesis.