Studies using lectins to determine mineral interactions with cellular membranes.
Chrysotile asbestos interacts with mucin-secreting cells of tracheal organ cultures, causing an increase in secretion of mucin into the culture medium. This response occurs in the absence of obvious morphologic damage to tracheal epithelial cells. We speculated that asbestos-induced hypersecretion was regulated by the interaction of fibers with specific carbohydrate residues on the cell surface. To test this hypothesis, lectins, i.e., proteins with a high affinity for mono- and oligosaccharides on the plasma membrane, were added to tissues 30 min before addition of chrysotile. Secretion of mucin into the medium was then determined over a 2-hr period by using incorporation of 3H-glucosamine. Blocking of alpha-D-mannose and alpha-D-glucose residues inhibited chrysotile-induced hypersecretion (p less than 0.05), whereas lectins blocking residues of alpha-D-N-acetylgalactosamine, beta-D-N-acetylglucosamine, alpha-L-fucose and sialic acids were ineffective. Preincubation of cultures with carboxypeptidase A or phospholipase A2, but not with neuraminidase, diminished mucin secretion caused by chrysotile. To determine if the positive surface charge of chrysotile was important in interaction with mucin cells, we examined comparatively the effects of various polycations (cationic ferritin, polylysine, DEAE-dextran) and chrysotile after leaching of fibers to remove Mg2+. Although use of polycations enhanced secretion of mucin, effects were not as striking as those observed with chrysotile. In contrast, leached chrysotile failed to elicit a hypersecretory response. These results suggest the interaction of a positively charged component (presumably Mg2+) of chrysotile with glycolipids and glycoproteins containing terminal residues of alpha-D-mannose or alpha-D-glucose.
D000818:Animals; D001194:Asbestos / Q000633:toxicity; D017632:Asbestos, Serpentine; D002268:Carboxypeptidases / Q000494:pharmacology; D043422:Carboxypeptidases A; D002412:Cations / Q000633:toxicity; D002462:Cell Membrane / Q000187:drug effects*; D037102:Lectins / Q000494:pharmacology; D008297:Male; D008903:Minerals / Q000633:toxicity*; D009077:Mucins / Q000378:metabolism; D009924:Organ Culture Techniques; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D014132:Trachea
D017632:Asbestos, Serpentine; D002412:Cations; D037102:Lectins; D008903:Minerals; D009077:Mucins; D001194:Asbestos; D010741:Phospholipases A; D054467:Phospholipases A2; D002268:Carboxypeptidases; D043422:Carboxypeptidases A