Pleiotropic role of lyn kinase in leukotriene B 4 –induced eosinophil activation

The authors have examined the role of the src-family of protein tyrosine kinases in leukotriene B 4 (LTB 4 )–induced activation of guinea-pig eosinophils. Western blot analysis identified the src-like protein tyrosine kinases p53 lyn, p56 lyn, p56/59 hck, p55 fgr, and p56 lck whereas p60 src, p62 yes, p55 blk, and p59 fyn were not detected. LTB 4 promoted a rapid increase in p53/56 lyn activity in eosinophils, which peaked at 5 seconds and remained elevated at 60 seconds; hck, fgr, and lck were not activated. A role for p53/56 lyn in eosinophil activation was investigated with the use of the src-selective inhibitor PP1 (1 μmol/L to 10 μmol/L), which attenuated LTB 4 -stimulated p53/56 lyn activity and the phosphorylation of extracellular signal-regulated kinase–2 in intact cells. At comparable concentrations, PP1 was also shown to attenuate LTB 4 -induced nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase activation, chemotaxis, and Ca ++ -dependent [ 3 H]arachidonic acid (AA) release. Moreover, an inhibitor of mitogen-activated protein kinase kinase-1, PD 098059, significantly inhibited LTB 4 -induced chemotaxis but had no effect on oxidant production or [ 3 H]AA release. Collectively, these results implicate lyn kinase in LTB 4 -induced eosinophil activation through the recruitment of divergent cell-signaling pathways.