Induction of superoxide anion production from monocytes and neutrophils by activated platelets through the P-selectin–sialyl Lewis X interaction

Activated platelets expressing P-selectin on their surface are known to adhere to monocytes and neutrophils. We examined the possibility that the leukocytes were activated by their adhesion to activated platelets and demonstrated that P-selectin-dependent platelet adhesion to neutrophils and monocytes induced production of extracellular superoxide anion (O2-) by these leukocytes. Leukocyte membrane glycoproteins containing Ser/Thr-linked carbohydrate chains were responsible for the signal reception leading to the leukocyte activation. Cytokines were shown to influence these processes. For example, treatments of neutrophils with interleukin-8 (IL-8) or granulocyte colony-stimulating factor (G-CSF) potentiated the P-selectin-induced O2- production. Furthermore, interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) induced surface expression of P-selectin on platelets in the presence of a low concentration of thrombin and consequently enhanced their adhesion capacity to leukocytes. These results indicated that the adhesion of activated platelets to the leukocytes through the interaction between P-selectin and its carbohydrate ligand, sialyl Lewis X (LeX), was a crucial step for the activation of leukocyte function and supported the notion that activated platelets were actively involved in the inflammatory processes.