title: The effects of carcinogenic methylcholanthrene on carbohydrate residues of NK cells.
abstract: The present study examines the effect of methylcholanthrene (MCA), a a carcinogenic polycyclic hydrocarbon, on the carbohydrate receptor determinants (RD) on natural killer (NK) cell surface using the bead-coupled lectin assay. Murine NK cells exhibited different degrees of preferential binding to the specific lectins tested. Of the ten lectins tested, five exhibited a positive binding affinity while the remaining five exhibited no or insignificant binding. NK cells bind to beads derivatized with mannose specific lectins: Concanavalin A (Con A), Lens culinaris, and Pisum sativum. NK cells also bind to other lectin beads such as Triticum vulgaris (GalNac) and Vicia villosa (D-GlcNAc). All these lectin beads exhibited greater than 90% adhesion. The underivatized control beads exhibited no NK binding. The NK cells that were exposed to MCA for 2 h demonstrated a significant decrease in lectin bead-cell coupling in a dose dependent manner. MCA (10 micrograms/mL) caused a 17.8%, 40% and 4.7% decrease in binding affinity when introduced to the mannose specific lectins; Con A, L. culinaris and P. sativum beads, respectively. The binding of T. vulgaris and V. villosa to NK cells was inhibited (23.4% and 28%) by MCA treatment. An increase in the dose to 20 micrograms/mL resulted in a greater inhibition in binding affinity towards lectin beads. Con A, 35.3%, L. culinaris, 62.6%, P. sativum, 30.9%, T. vulgaris, 44.2% and V. villosa, 46.2%. The effect of MCA activation and cytotoxic response. Hydrolysis of PI metabolites (PIP and PIP2) cause generation of secondary messenger: inositol-1,4,5-triphosphate and diacylglycerol, both of which elicit an immune response through their products (Ca2+ and PKC) respectively. Identification of the relationship between receptor level, induction of second messenger and cytotoxic activity may resolve the molecular basis of suppression of NK cytotoxicity by MCA and other PAH compounds.
authors.affiliation: Drew University of Medicine and Science, Department of Otolaryngology, Los Angeles, CA 90059, USA. mghoneum@ucla.edu
authors.forename: M
authors.initials: M
authors.lastname: Ghoneum
authors.forename: A
authors.initials: A
authors.lastname: Vojdani
authors.forename: A
authors.initials: A
authors.lastname: Banionis
authors.forename: S
authors.initials: S
authors.lastname: Oppenheimer
authors.forename: N
authors.initials: N
authors.lastname: Lagos
authors.forename: G
authors.initials: G
authors.lastname: Gill
mesh_terms: D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D002273:Carcinogens / Q000633:toxicity*; D004121:Dimethyl Sulfoxide; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D037102:Lectins / Q000737:chemistry; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis
chemical_list: D002241:Carbohydrates; D002273:Carcinogens; D037102:Lectins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D008748:Methylcholanthrene; D004121:Dimethyl Sulfoxide