The authors have examined the role of the src-family of protein tyrosine kinases in leukotriene B4(LTB4)–induced activation of guinea-pig eosinophils. Western blot analysis identified the src-like protein tyrosine kinases p53lyn, p56lyn, p56/59hck, p55fgr, and p56lck whereas p60src, p62yes, p55blk, and p59fyn were not detected. LTB4 promoted a rapid increase in p53/56lyn activity in eosinophils, which peaked at 5 seconds and remained elevated at 60 seconds; hck, fgr, and lck were not activated. A role for p53/56lyn in eosinophil activation was investigated with the use of the src-selective inhibitor PP1 (1 μmol/L to 10 μmol/L), which attenuated LTB4-stimulated p53/56lyn activity and the phosphorylation of extracellular signal-regulated kinase–2 in intact cells. At comparable concentrations, PP1 was also shown to attenuate LTB4-induced nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase activation, chemotaxis, and Ca++-dependent [3H]arachidonic acid (AA) release. Moreover, an inhibitor of mitogen-activated protein kinase kinase-1, PD 098059, significantly inhibited LTB4-induced chemotaxis but had no effect on oxidant production or [3H]AA release. Collectively, these results implicate lyn kinase in LTB4-induced eosinophil activation through the recruitment of divergent cell-signaling pathways.
Bifunctional Role of Protein Tyrosine Kinases in Late Preconditioning Against Myocardial Stunning in Conscious Rabbits