Relaxin Inhibits the Activation of Human Neutrophils: Involvement of the Nitric Oxide Pathway

In animal models of inflammation, the pregnancy hormone relaxin was shown to reduce the recruitment of leukocytes, especially neutrophils, in inflamed tissues. The current study was designed to clarify whether relaxin could inhibit activation of isolated human neutrophils and, if so, whether the nitric oxide (NO) biosynthetic pathway was involved, as occurs in other relaxin targets. Human neutrophils were preincubated with 1, 10, and 100 nmol/liter porcine relaxin for 1 h before activation with N-formyl-Met-Leu-Phe (10 μmol/liter) or phorbol-12-myristate-13-acetate (0.1 μmol/liter). In selected experiments, the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA, 100 μmol/liter) was added to the samples 30 min before relaxin. In other experiments, chemically inactivated relaxin (10 nmol/liter) was substituted for authentic relaxin. Untreated, nonactivated neutrophils were the controls. Relaxin reduced significantly and in a concentration-dependent fashion the expression of the surface activation marker...