Induction of histamine release from rat peritoneal mast cells by histatins

Human salivary histatins (Hsts), which belong to a salivary polypeptide fam ily, have potent antifungal activity against Candida albicans and Cryptococ cus neoformans, and are expected to be useful as therapeutic reagents again st Candida species. However, little is known about the effect of Hsts on ho st immune systems. Thus we conducted a series of in vitro experiments with rat mast cells to determine whether histatin 5 (Hst 5) or histatin 8 (Hst 8 ) has a histamine-releasing effect on mast cells. Both Hst 5 and Hst 8 indu ced histamine release from rat peritoneal mast cells in a dose-dependent ma nner (10(-9) to 10(-5) m). Hst 5 had a stronger releasing effect than Hst 8 . The histamine release induced by Hst 5 (10(-6) M) was increased by the pr esence of 0.5 mm Ca2+, but decreased by 2 mm Ca2+. Alternatively, the hista mine release induced by Hst 8 (10(-6) M) was inhibited by the presence of C a2+ (0.5 to 2 mm). These results suggest that Hsts have limited usefulness as therapeutic agents due to induction of histamine release from mast cells .