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.
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.
Wenzel-Seifert
K
K
Institut für Pharmakologíe, Freie Universität Berlin, Germany.
Lentzen
H
H
Seifert
R
R
D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D015936:Complement C5a / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D028321:Plant Preparations; D010940:Plant Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology*; D054790:Ribosome Inactivating Proteins, Type 2; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology*
D015703:Antigens, CD; D037102:Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011969:Receptors, Histamine H1; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C488862:mistletoe lectin I; C009674:ribosome inactivating protein, Viscum; D015936:Complement C5a; D002118:Calcium