Leukotriene D-4-induced Rho-mediated actin reorganization in human bronchial smooth muscle cells

We investigated the role of cysteinyl leukotriene (CysLT) receptors an leuk otriene D-4-induced actin reorganization and the signaling pathways of the response in human bronchial smooth muscle cells. The effects of leukotriene D-4 on actin reorganization in human bronchial smooth muscle cells were ev aluated by dual-fluorescence labeling of filamentous (F) and monomeric (G) actin with fluorescein isothiocyanate (FITC)-labeled phalloidin and Texas R ed-labeled DNase I, respectively. Leukotriene D-4 (100 nM) induced actin re organization in the presence and absence of extracellular Ca2+. The CysLT t ype 1 (CysLT(1)) receptor antagonist ONO 1078 (4-oxa-8(-)[p-(4-phenylbutylo xy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate) inhibited leukotriene D-4-induced actin reorganization. Pretreatment with pertussis t oxin, C3 exoenzyme, or tyrosine kinase inhibitors significantly reduced leu kotriene D-4-induced actin reorganization. However, phosphatidylinositol-3- kinase and protein kinase C inhibitors had little effect on these responses . These results suggest that leukotriene D-4-induced actin reorganization i n human bronchial smooth muscle cells is extremely dependent on the CysLT(1 ) receptor coupled with pertussis toxin-sensitive G protein, Rho GTPases an d tyrosine phosphorylation pathways. (C) 2001 Published by Elsevier Science B.V.