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DIFFERENTIATION-LINKED ACTIVATION OF THE RESPIRATORY BURST IN A MONOCYTIC CELL-LINE (U937) VIA FC-GAMMA-RII - A STUDY OF ACTIVATION PATHWAYS AND THEIR REGULATION

ROBERTS, PJ; DEVALIA, V; FAINT, R; PIZZEY, A; BAINTON, AL; THOMAS, NSB; PILKINGTON, GR; (1991) DIFFERENTIATION-LINKED ACTIVATION OF THE RESPIRATORY BURST IN A MONOCYTIC CELL-LINE (U937) VIA FC-GAMMA-RII - A STUDY OF ACTIVATION PATHWAYS AND THEIR REGULATION. J IMMUNOL , 147 (9) 3104 - 3115.

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Abstract

Activation of the respiratory burst in the monocytic cell line U937 by cross-linking human 40-kDa FcR for IgG (Fc-gamma-RII) with the IgG1 mAb, CIKM5, is dependent on the maturation state of the cell. Addition of anti-Fc-gamma-RII to undifferentiated cells does not activate the respiratory burst but differentiation with human rIFN-gamma (200 U/ml) for 13 to 15 days results in maximal stimulation by this agonist, with half-maximal responses in cells incubated for 10 to 12 days. During maturation the development of responsiveness to cross-linking Fc-gamma-RII occurs later than the development of responsiveness to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (maximal responses at 7 to 9 days), or the chemotactic peptide FMLP (half-maximal responses at 7 to 9 days). The late development of maximal Fc-gamma-RII responses is not associated with either increased Fc-gamma-RII expression, enhanced calcium mobilization induced by anti-Fc-gamma-RII, changes in protein kinase C activity (PKC) or a switch in PKC isotype expression. Activation of the respiratory burst via Fc-gamma-RII may not be mediated by activation of PKC as the kinase inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride inhibited the FC-gamma-RII response by less than 20% at concentrations which inhibit the 12-O-tetradecanoylphorbol-13-acetate-induced respiratory burst by more than 80%. IFN-gamma U937 cells did not metabolize incorporated arachidonate into eicosanoids when stimulated with anti-Fc-gamma-RII, suggesting that eicosanoids do not mediate activation of the respiratory burst, and this was confirmed by the lack of inhibition by the specific 5'-lipoxygenase and glutathione S-transferase inhibitor, piriprost, and the cyclo-oxygenase inhibitor, indomethacin. In addition there was no significant release of radiolabeled arachidonate in response to anti-Fc-gamma-RII. The response to anti-Fc-gamma-RII is inhibited by pertussis toxin, suggesting that signal transduction is via a GTP-binding protein. Agents that elevate intracellular cAMP increased the magnitude of the cAMP transients stimulated by anti-Fc-gamma-RII and also inhibited the respiratory burst. FMLP responses showed a similar pattern of sensitivity to this range of inhibitors, suggesting that both Fc-gamma-RII and FMLP receptor share common regulatory mechanisms. However, the termination of the respiratory burst activated via Fc-gamma-RII and FMLP receptor is independently regulated, in that after FMLP-induced activation there is no subsequent inhibition of the Fc-gamma-RII-mediated response and vice versa.

Type: Article
Title: DIFFERENTIATION-LINKED ACTIVATION OF THE RESPIRATORY BURST IN A MONOCYTIC CELL-LINE (U937) VIA FC-GAMMA-RII - A STUDY OF ACTIVATION PATHWAYS AND THEIR REGULATION
Keywords: PROTEIN KINASE-C, SUPEROXIDE ANION PRODUCTION, HUMAN-NEUTROPHILS, CROSS-LINKING, INTERFERON-GAMMA, NADPH OXIDASE, CHEMOTACTIC PEPTIDES, GENERATING OXIDASE, ARACHIDONIC-ACID, IFN-GAMMA
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/120405
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