Crystal-induced protein tyrosine phosphorylation in neutrophils and the effect of a tyrosine kinase inhibitor on neutrophil responses.
A specific tyrosine kinase inhibitor, methyl 2,5-dihydroxycinnamate (mDHC), has been used to investigate the role of tyrosine kinases in monosodium urate monohydrate and calcium pyrophosphate dihydrate (CPPD) crystal-induced neutrophil activation. Both uncoated and plasma protein-coated CPPD crystals increased protein tyrosine phosphorylation in human neutrophils. Neutrophils pretreated with mDHC or control neutrophils were stimulated by plasma-opsonized CPPD, uncoated CPPD, or uncoated monosodium urate monohydrate, and chemiluminescence, superoxide generation, intracellular calcium concentration, degranulation (myeloperoxidase and lysozyme release), and protein tyrosine phosphorylation were monitored. mDHC strongly inhibited all neutrophil responses and tyrosine phosphorylation was reduced to the basal levels seen in control unstimulated neutrophils. The possible role of tyrosine kinases in the regulation of crystal-induced neutrophil activation is discussed.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
H M
HM
Burt
J K
JK
Jackson
P
P
Dryden
H
H
Salari
D002118:Calcium / Q000032:analysis; D002131:Calcium Pyrophosphate / Q000494:pharmacology*; D015550:Cell Degranulation; D002478:Cells, Cultured; D003460:Crystallization; D006801:Humans; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D014527:Uric Acid / Q000494:pharmacology*
D013481:Superoxides; D014527:Uric Acid; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D002118:Calcium; D002131:Calcium Pyrophosphate