In U-937 promonocytes, misteltoe lectin I increases basal [Ca2+]i, enhances histamine H1- and complement C5a-receptor-mediated rises in [Ca2+]i, and induces cell death

Abstract

Mistletoe lectin I (ML I) from Viscum album inhibits cell growth and induces apoptosis (programmed cell death) in several cell types. Because increases in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) constitute a signal for the induction of apoptosis, we studied the effects of ML I on basal [Ca²⁺]_i, receptor-mediated rises in [Ca²⁺]_i and cell viability, using human U-937 promonocytes as model system. Treatment of U-937 cells with ML I (30–100 ng/ml) significantly increased basal [Ca²⁺]_i. ML I (10–30 ng/ml) enhanced histamine-induced rises in [Ca²⁺]_i up to five-fold. The effect of histamine was inhibited by clemastine but not by famotidine, indicative for its mediation via H₁-receptors. ML I additionally enhanced the stimulatory effect of complement C5a on [Ca²⁺]_i, whereas the effect of ATP was unaffected. ML I did not induce responsiveness of U-937 cells towards a bacteria-derived chemotactic peptide. ML I up to 10 ng/ml did not affect cell viability and growth of U-937 cells. ML I at 30 ng/ml moderately inhibited cell growth and reduced cell viability. At 100 ng/ml, ML I was strongly cytotoxic. Our data support the view that Ca²⁺ plays a role as intracellular signal molecule in the induction of apoptosis and point to an accelerating role of H₁- and C5a-receptors in the regulation of this process.