Premium
Inhibition of human neutrophil responses by α‐cyano‐3,4‐dihydroxythiocinnamamide; a protein‐tyrosine kinase inhibitor
Author(s) -
Dryden Peter,
Duronio Vincent,
Martin Liana,
Hudson Alan T.,
Salari Hassan
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14391.x
Subject(s) - tyrosine kinase inhibitor , tyrosine , pharmacology , tyrosine kinase , biology , chemistry , medicine , biochemistry , signal transduction , cancer
1 Activation of neutrophils results in increased tyrosine phosphorylation of several proteins that may have important roles in receptor/effector coupling. In this study, the effect of a protein tyrosine kinase inhibitor on receptor‐mediated neutrophil activation by platelet‐activating factor (PAF), leukotriene, B 4 (LTB 4 ) and N‐formylmethionylleucylphenylalanine (FMLP) is investigated. 2 α‐Cyano‐3,4‐dihydroxythiocinnamamide dose‐dependently inhibited intracellular calcium release and superoxide generation from human neutrophils activated by 1 μ m LTB 4 , PAF, and FMLP. 3 In the presence of cytochalasin B, FMLP stimulated elastase release from neutrophils was also inhibited to unstimulated levels by 5 min pretreatment with α‐cyano,3,4‐dihydroxythiocinnamamide. 4 The inhibitory action of α‐cyano‐3,4‐dihydroxythiocinnamamide was found to be at or upstream of phospholipase C activation, blocking both phosphatidylinositol hydrolysis and protein kinase C activation. α‐Cyano‐3,4‐dihydroxythiocinnamamide did not affect agonist receptor binding sites or receptor affinity in neutrophils. 5 Immunoblot analysis demonstrated the tyrosine phosphorylation of proteins of 41, 56, 66, and 104 kDa in neutrophils treated with agonists. Treatment of neutrophils with α‐cyano‐3,4‐dihydroxythiocinnamamide prior to stimulation with chemoattractants reduced tyrosine phosphorylation of the above phosphoproteins. 6 These results indicate that α‐cyano‐3,4‐dihydroxythiocinnamamide might be a useful agent in characterizing the essential proteins and biochemical pathways that regulate neutrophil activation.