Cytokine Secretion from Human Monocytes Potentiated by P-Selectin-Mediated Cell Adhesion

Background/Aim: P-selectin is a carbohydrate-recognizing cell adhesion molecule expressed on activated platelets and endothelial cells. It plays a crucial role in the recruitment of leukocytes to inflammatory and hemorrhagic sites. Cell adhesion mediated by P-selectin induces leukocyte activation, such as the generation of reactive oxygen species and the expression of blood coagulation factors. We assessed how P-selectin-mediated cell adhesion affects cytokine secretion from monocytes. Methods: Human peripheral blood monocytes were cultured in a plate that had been coated with P-selectin purified from human platelets, and cytokines released in the culture supernatant from monocytes were determined by ELISA. Results: The secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, IL-12 and macrophage inflammatory protein-1 beta increased 3- to 10-fold in response to P-selectin compared with unstimulated monocytes. We next examined the effects of cytokine treatment of monocytes on their susceptibility to P-selectin. The secretion of TNF-alpha from monocytes in response to P-selectin was increased when monocytes were preincubated with granulocyte/macrophage colony-stimulating factor, monocyte chemotactic protein-1 or interferon-gamma (IFN-gamma); IFN-gamma was the most effective in potentiating TNF-gamma secretion from monocytes. Conclusion: These results suggest that the interaction of monocytes with P-selectin plays an important role not only in their trafficking but also in the regulation of cytokine production by these cells. Copyright (C) 2012 S. Karger AG, Basel