RESUMO
BAY 41-2272 is a guanylyl cyclase (GC) stimulator derived from YC-1 (3-[(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole]). Previous studies by our group showed that BAY 41-2272 activates human monocytes via soluble guanylyl cyclase (sGC) and cGMP. In this study, we investigated the effect of BAY 41-2272 on human neutrophil function and found that 30⯵M BAY 41-2272 inhibits neutrophil migration (1.82-fold lower than FMLP, Pâ¯<â¯0.05 by one-way ANOVA followed by Tukey's test), oxidative burst (1.70-fold lower than PMA, Pâ¯<â¯0.05 by one-way ANOVA followed by Tukey's test), and IL-8 cytokine production (1.80-fold lower than PMA, Pâ¯<â¯0.05 by one-way ANOVA followed by Tukey's test). Our results suggest that these effects are independent of the sGC pathway but dependent instead on cGMP production, as the response induced by 30⯵M BAY 41-2272 was 6.40-fold greater than that observed in our negative control (Pâ¯<â¯0.05 by parametric t-test). 1H-[1, 2, 4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), which is an irreversible inhibitor of sGC, was unable to reverse the effects of BAY 41-2272 on human neutrophils, indicating that this drug acts independently of sGC. Our results confirm the immunomodulatory effect of BAY 41-2272 on human neutrophils.