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 micromol/L to 10 micromol/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.
Lynch
O T
OT
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
Giembycz
M A
MA
Daniels
I
I
Barnes
P J
PJ
Lindsay
M A
MA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D007975:Leukotriene B4; D016718:Arachidonic Acid; D019255:NADPH Oxidases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium