BAY 41-2272 inhibits human neutrophil functions

摘要

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 mu M BAY 41-2272 inhibits neutrophil migration (1.82-fold lower than FMLP, P < 0.05 by one-way ANOVA followed by Tukey's test), oxidative burst (1.70-fold lower than PMA, P < 0.05 by one-way ANOVA followed by Tukey's test), and IL-8 cytokine production (1.80-fold lower than PMA, P < 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 pM BAY 41-2272 was 6.40-fold greater than that observed in our negative control (P < 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.