Inhibitory effects of relaxin on human basophils activated by stimulation of the Fcε receptor. The role of nitric oxide

Abstract This study investigates whether relaxin (RLX), a hormone previously shown to inhibit mast cell function and to stimulate endogenous nitric oxide (NO) biosynthesis, counteracts the activation of isolated human basophils stimulated with anti-IgE or phorbol ester, and, if so, whether NO is involved. RLX reduced dose-dependently the expression of the activation marker CD63, the release of histamine and the rise of intracellular Ca 2+ levels which triggers granule release by stimulated basophils. RLX also blunts the ultrastructural signs of anaphylactic granule release. The effects of RLX appear to depend upon activation of Ca 2+ /calmodulin-dependent NO synthase and endogenous NO production. They were reproduced by the NO donor sodium nitroprusside (SNP) and were reverted by the NO synthase inhibitor N ω -monomethyl- l -arginine, or by the NO scavenger oxyhemoglobin, or by blocking the NO physiological target guanylate cyclase with ODQ. In conclusion, RLX appears to play a role in down-regulating basophil function upon immunologic and nonimmunologic activation.