INHIBITION OF CRYSTAL-INDUCED NEUTROPHIL ACTIVATION BY A PROTEIN-TYROSINE KINASE INHIBITOR

The objective of this work was to investigate the role of tyrosine kin ase in monosodium urate monohydrate (MSUM) and calcium pyrophosphate d ihydrate (CPPD) crystal-induced neutrophil activation using the tyrosi ne kinase inhibitor lavendustin C (LVC). Human neutrophils pretreated with LVC at concentrations between 10 and 150 mu M or control neutroph ils were stimulated by plasma-coated CPPD or uncoated MSUM, and chemil uminescence, superoxide generation, intracellular calcium concentratio n, and degranulation (myeloperoxidase and lysozyme release) were monit ored with time. LVC strongly inhibited chemiluminescence, superoxide a nion generation, myeloperoxidase and lysozyme release, and calcium mob ilization. After 1-min crystal-neutrophil incubations, neutrophil cyto solic fractions showed extensive inhibition of tyrosine kinase activit y by LVC. We conclude that the inhibition of neutrophil responses to c rystal stimulation, by the protein tyrosine kinase inhibitor LVC, prov ides evidence that supports the involvement of tyrosine kinases in cry stal-induced neutrophil activation.