MONOCHLORAMINE INHIBITS PHORBOL ESTER-INDUCIBLE NEUTROPHIL RESPIRATORY BURST ACTIVATION AND T-CELL INTERLEUKIN-2 RECEPTOR EXPRESSION BY INHIBITING INDUCIBLE PROTEIN-KINASE-C ACTIVITY

Monochloramine derivatives are long lived physiological oxidants produ ced by neutrophils during the respiratory burst, The effects of chemic ally prepared monochloramine (NH2Cl) on protein kinase C (PKC) and PKC -mediated cellular responses were studied in elicited rat peritoneal n eutrophils and human Jurkat T cells, Neutrophils pretreated with NH2Cl (30-50 mu M) showed a marked decrease in the respiratory burst activi ty induced by phorbol 12-myristate 13-acetate (PMA), which is a potent PKC activator. These cells, however, were viable and showed a complet e respiratory burst upon arachidonic acid stimulation, which induces t he respiratory burst by a PKC-independent mechanism, The NH2Cl-treated neutrophils showed a decrease in both PRC activity and PMA-induced ph osphorylation of a 47-kDa protein, which corresponds to the cytosolic factor of NADPH oxidase, p47(phox). Jurkat T cells pretreated with NH2 Cl (20-70 mu M) showed a decrease in the expression of the interleukin -a receptor a chain following PMA stimulation. This was also accompani ed by a decrease in both PKC activity and nuclear transcription factor -kappa B activation, also without loss of cell viability, These result s show that NH2Cl inhibits PKC-mediated cellular responses through inh ibition of the inducible PKC activity.