Abstract
The effects of cbz-leucine-tyrosine-chloromethylketone(2LYCK), an inhibitor of chymotrypsin, were investigated in the activation pathways of human neutrophil respiratory burst. At 10 μM zLYCK showed a parallel inhibition of superoxide production stimulated with the chemoattractant formyl-methionyl-leucyl phenylalanine (FMLP) and chymotrypsin-like activity ot human neutrophils. By contrast superoxide production induced by phorbol mirystate acetate (PMA) was minimally affected by zLYCK. The known transduction pathways triggered by FMLP were analyzed. zLYCK did not affect either FMLP-induced cytosolic free calcium transient, inositol 1,4,5 triphosphate formation nor the PMA-induced phosphorylation of the 47 kD substrate of protein kinase c. zLYCK did not affect the activity of protein kinase c extracted from neutrophils. The activity ot the NADPH oxidase tested with active membranes from stimulated neutrophils or in a cell-tree-system was not inhibited by zLYCK. We conclude that 1) zLYCK inhibits superoxide production through the inhibition of a chymotrypsin-like protease of the neutrophil 2) zLYCK inhibits FMLP-induced activation of NADPH oxidase through a pathway independent of PtdInsP2 breakdwon and cytosolic free calcium 3) zLYCK may prove an useful probe for the characterization of its target protease in neutrophil activation.
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Gervaix, A., Kessels, G., Suter, S. et al. 117 THE CHYMOTRYPSIN INHIBITOR CARBOBENZYLOXY-LEUCINE TYROSINE-CHLOROMETHYLKETONE (zLYCK) INTERFERES WITH THE NEUTROPHIL RESPIRATORY BURST MEDIATED BY A SIGNALING PATHWAY INDEPENDENT OF PtdinsP2 BREAKDOWN AND CYTOSOLIC FREE CALCIUM. Pediatr Res 30, 647 (1991). https://doi.org/10.1203/00006450-199112000-00147
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DOI: https://doi.org/10.1203/00006450-199112000-00147