Inhibition of phospholipase D blocks activation of fibrinogen-adherent neutrophils by tumor necrosis factor.
Tumor necrosis factor stimulates fibrinogen-adherent neutrophils to produce a dramatic oxidative burst; the resulting superoxide and other products may contribute to tissue damage in severe infection. Inhibitors of the phospholipase D pathway blocked this activation without affecting cell adherence or nonspecific activation by phorbol myristate acetate. The phospholipase D pathway appears to be involved in the activation of adherent neutrophils by tumor necrosis factor, and this pathway may be a target for modulation of tumor necrosis factor's effects.
Frank
M O
MO
Department of Medicine, University of Virginia, School of Medicine, Charlottesville 22908.
Sullivan
G W
GW
Carper
H T
HT
Mandell
G L
GL
D002448:Cell Adhesion; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D005340:Fibrinogen; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate