ACTIVATION OF THE MACROPHAGE RESPIRATORY BURST BY PHORBOL-MYRISTATE ACETATE - EVIDENCE FOR BOTH TYROSINE KINASE-DEPENDENT AND KINASE-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 bath tyrosine-kinase-dependent and -independent pathways.