Activation of the macrophage respiratory burst by phorbol myristate acetate: evidence for both tyrosine-kinase-dependent and -independent pathways.
We have investigated the relationship between tyrosine phosphorylation and respiratory-burst activity in murine bone-marrow-derived macrophages (BMM) stimulated with phorbol myristate acetate (PMA). In unprimed BMM, a good correlation was observed between the net level of tyrosine phosphorylation and the activity of the respiratory burst. The phosphotyrosine phosphatase inhibitor, vanadate, enhanced both tyrosine phosphorylation and respiratory-burst activity triggered by PMA. Furthermore, the tyrosine kinase inhibitor, ST638, abolished both tyrosine phosphorylation and respiratory-burst activity stimulated by PMA. However, in BMM primed by preexposure to TNF alpha, the correlation between net tyrosine phosphorylation and respiratory-burst activity triggered by PMA was not maintained. ST638 was found to only partially inhibit the PMA-triggered respiratory burst under conditions where PMA-stimulated tyrosine phosphorylation was abolished. We conclude that PMA can activate the macrophage respiratory burst by both tyrosine-kinase-dependent and -independent pathways.
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Australia.
S P
SP
Green
W A
WA
Phillips
D000818:Animals; D002934:Cinnamates / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013440:Sulfides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
D002934:Cinnamates; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; C060747:ST 638; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate