TY - JOUR 
A1 - Milara, Javier
AU - Martínez Losa, Maleles
AU - Sanz García, Celia
AU - Almudéver, Patricia
AU - Peiró, Teresa
AU - Serrano, Adela
AU - Morcillo, Esteban
AU - Zaragoza, Cristóbal
AU - Cortijo, Julio
T1 - Bafetinib inhibits functional responses of human eosinophils in vitro
Y1 - 2013
SN - 00142999
UR - http://hdl.handle.net/11268/5213
AB - Eosinophils play a prominent role in the process of allergic inflammation. Non-receptor associated Lyn tyrosine kinases generate key initial signals in eosinophils. Bafetinib, a specific Abl/Lyn tyrosine kinase inhibitor has shown a potent antiproliferative activity in leukemic cells, but its effects on eosinophils have not been reported. Therefore, we studied the effects of bafetinib on functional and mechanistic responses of isolated human eosinophils. Bafetinib was more potent than non-specific tyrosin kinase comparators genistein and tyrphostin inhibiting superoxide anion triggered by N-formyl-Met-Leu-Phe (fMLF; 100 nM) (−log IC50=7.25±0.04 M; 6.1±0.04 M; and 6.55±0.03 M, respectively). Bafetinib, genistein and tyrphostin did not modify the [Ca2+]i responses to fMLF. Bafetinib inhibited the release of EPO induced by fMLF with higher potency than genistein and tyrphostin (−log IC50=7.24±0.09 M; 5.36±0.28 M; and 5.37±0.19 M, respectively), and nearly suppressed LTC4, ECP and chemotaxis. Bafetinib, genistein and tyrphostin did not change constitutive apoptosis. However bafetinib inhibited the ability of granulocyte–monocyte colony-stimulating factor to prevent apoptosis. The activation of Lyn tyrosine kinase, p-ERK1/2 and p-38 induced by fMLF was suppressed by bafetinib and attenuated by genistein and tyrphostin. In conclusion, bafetinib inhibits oxidative burst and generation of inflammatory mediators, and reverses the eosinophil survival. Therefore, future anti-allergic therapies based on bafetinib, could help to suppress excessive inflammatory response of eosinophils at inflammatory sites.
KW - Farmacología
KW - Farmacología
LA - spa
ER -