Induction of superoxide anion production from monocytes an 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.
Tsuji
T
T
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Nagata
K
K
Koike
J
J
Todoroki
N
N
Irimura
T
T
D001792:Blood Platelets / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009844:Oligosaccharides / Q000494:pharmacology; D019007:P-Selectin; D015539:Platelet Activation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D000080506:Sialyl Lewis X Antigen; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009844:Oligosaccharides; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D000080506:Sialyl Lewis X Antigen; D013481:Superoxides