Midkine induces histamine release from mast cells and the immediate cutaneous response

Midkine is a product of a retinoic acid-responsive gene and exerts a variety of biological activities. The aim of our investigation is to determine whether human midkine have histamine-releasing effects on mast cells, and to show the evidence of the inflammation induced by midkine. Midkine induced histamine release from rat peritoneal mast cells with a rapid response in a dose-dependent manner. Extracellular calcium inhibited the histamine release induced by midkine in a dose-dependent manner. Pertussis toxin and benzalkonium chloride inhibited the histamine release induced by midkine. Gi-proteins exert an effect on the histamine release of midkine. The immediate cutaneous response induced by midkine was positive. These results suggest that midkine may take part in some inflammation via histamine release from mast cells.