IN U-937 PROMONOCYTES, MISTELTOE LECTIN-I INCREASES BASAL [CA2(-1-RECEPTOR AND COMPLEMENT C5A-RECEPTOR MEDIATED RISES IN [CA2+](I), AND INDUCES CELL-DEATH()](I), ENHANCES HISTAMINE H)

Mistletoe lectin I (ML I) from Viscum album inhibits cell growth and i nduces apoptosis (programmed cell death) in several cell types. Becaus e increases in cytosolic Ca2+ concentration ([Ca2+](i)) constitute a s ignal for the induction of apoptosis, we studied the effects of ML I o n basal [Ca2+](i), receptor-mediated rises in [Ca2+](i) and cell viabi lity, using human U-937 promonocytes as model system. Treatment of U-9 37 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 b ut not by famotidine, indicative for its mediation via H-1-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 ind uce responsiveness of U-937 cells towards a bacteria-derived chemotact ic peptide. ML I up to 10 ng/ml did not affect cell viability and grow th of U-937 cells. ML I at 30 ng/ml moderately inhibited cell growth a nd reduced cell viability. At 100 ng/ml, ML I was strongly cytotoxic. Our data support the view that Ca2+ plays a role as intracellular sign al molecule in the induction of apoptosis and point to an accelerating role of H-1- and C5a-receptors in the regulation of this process.