Zymosan-triggered tyrosine phosphorylation in mouse bone-marrow-derived macrophages is enhanced by respiratory-burst priming agents.
We have investigated the relationship between tyrosine phosphorylation and respiratory-burst activity in mouse bone-marrow-derived macrophages (BMM). We demonstrate that zymosan, an agent known to trigger the macrophage respiratory burst, also triggers the activation of tyrosine kinase activity, resulting in rapid tyrosine phosphorylation on numerous proteins, and provide evidence for the role of tyrosine phosphorylation in the triggering of the BMM respiratory burst. Agents, such as tumour necrosis factor alpha (TNF alpha), interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS), which prime the macrophage for an enhanced zymosan-triggered respiratory burst, increase tyrosine phosphorylation triggered by zymosan. The zymosan-triggered tyrosine phosphorylation and respiratory-burst activity were partially suppressed by the tyrosine kinase inhibitors alpha-cyano-3-ethoxy-4-hydroxy-5-phenylmethylcinnamide (ST638) and herbimycin A. In addition, pre-exposure of BMM to vanadate, a phosphotyrosine phosphatase inhibitor, greatly enhanced the ability of zymosan to induce tyrosine phosphorylation and trigger the respiratory burst. These data highlight the importance of the balance between tyrosine kinase and phosphotyrosine phosphatase activity in determining the ultimate level of tyrosine phosphorylation in BMM and suggest that zymosan-triggered tyrosine phosphorylation is an important biochemical signal for triggering of the respiratory burst.
D000818:Animals; D016227:Benzoquinones; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D016897:Respiratory Burst; D017828:Rifabutin / Q000031:analogs & derivatives; D013440:Sulfides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
D016227:Benzoquinones; D002934:Cinnamates; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; D011809:Quinones; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; C060747:ST 638; D017828:Rifabutin; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; C020754:herbimycin; D007371:Interferon-gamma; D015054:Zymosan; D011505:Protein-Tyrosine Kinases