Inflammation is a driving force behind various lethal pathological conditions, including atherosclerosis and cancer metastasis. Inflammatory mediators are keys that unlock the immune response via triggering interactions of leukocytes and vascular endothelial cells. Oxidized low density lipoprotein (OxLDL), lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-α), and histamine are all strong activators of the inflammatory response, and they can be simultaneously produced during various inflammatory disorders. This study focuses on investigating the cooperative effect of TNF-α and histamine, as well as OxLDL and histamine on monocyte-endothelium interactions. Furthermore, the roles of LPS-activated monocytes and histamine in interactions of breast cancer cells with vascular endothelium are also explored. The results suggest that: 1) TNF-α and histamine have a synergistic effect on monocyte-endothelium interactions; 2) histamine cooperatively works with OxLDL to induce monocyte recruitment on endothelial cells; 3) OxLDL treated macrophages and mast cells respectively release TNF-α and histamine, which in turn synergistically increase the capture of monocytes by endothelial cells; 4) LPS activated monocytes secret TNF-α to activate endothelial cells and assist in adhesion of carcinoma cells to activated vascular endothelium; 5) exposure of activated endothelial cells to histamine exaggerates the carcinoma cell arrest, especially in the presence of LPS activated monocytes. In summary, this study implies that an increased risk of atherogenesis may be among the population affected by allergy or asthma and having lipid rich diet that leads to the production of TNF-α and OxLDL in body. It also highlights that the mechanism by which Gram-negative bacterial infection increases a risk of breast cancer metastasis through the cardiovascular system, and shows the necessity to develop better approaches for preventing this infection after surgical resection or before histamine combined IL-2 immune therapy in order to reduce a risk of cancer metastasis.
