Interactions of chrysotile and crocidolite asbestos with red blood cell membranes. Chrysotile binds to sialic acid.
Chrysotile and crocidolite are commonly used forms of asbestos. Hemolysis has been widely used as a test of membrane injury, and it has been shown previously that chrysotile causes rapid breakdown of red blood cells (RBCs), whereas crocidolite is only weakly hemolytic. A reasonable hypothesis set forth to explain the cytotoxic effects of chrysotile maintains that positively charged chrysotile fibers bind to negatively charged sialic acid residues on RBC membranes causing clustering of membrane proteins and increased cell permeability to Na and K ions. Our studies presented here provide two lines of evidence in direct support of this hypothesis. (a) Morphologic--Ultrastructural techniques showed that both chrysotile and crocidolite asbestos bind to and distort more than 85% of RBCs treated for 15 minutes. The distorting effects of chrysotile, but not crocidolite, were almost totally ablated by pretreating the cells with neuraminidase. In addition, gold-conjugated wheat germ agglutinin was used to label the distribution of sialic acid groups on RBC membranes. Pretreatment of the RBCs with chrysotile, but not crocidolite, reduced the number of gold-conjugated wheat germ agglutinin-labeled sites to less than 30% of the control level. (b) Biochemical--The thiobarbituric acid assay was used to determine the percentage of sialic acid that remained with the cell pellet after neuraminidase and/or asbestos treatment. Asbestos treatment alone caused no release of sialic acid from the cells. Neuraminidase treatment for 3.5 hours removed more than 80% of the sialic acid from cell surfaces. Chrysotile, but not crocidolite, asbestos prevented neuraminidase-mediated removal of sialic acid from RBCs. In addition, x-ray energy spectrometry of freeze-dried cells showed that RBCs distorted by chrysotile, but not by crocidolite, exhibited significant alterations in intracellular Na:K ratios. The morphologic and biochemical data strongly support the hypothesis that chrysotile asbestos binds to sialic acid groups on RBC membranes. Consequently, the sialic acid residues are redistributed on the surfaces of distorted cells which then are unable to maintain a normal Na:K balance with the surrounding medium.
D000818:Animals; D001194:Asbestos / Q000097:blood / Q000633:toxicity*; D017638:Asbestos, Crocidolite; D017632:Asbestos, Serpentine; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004913:Erythrocytes, Abnormal / Q000648:ultrastructure; D008565:Membrane Proteins / Q000097:blood; D009439:Neuraminidase / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D051381:Rats; D012794:Sialic Acids / Q000097:blood*; D012822:Silicon Dioxide / Q000633:toxicity; D012964:Sodium / Q000097:blood
D017632:Asbestos, Serpentine; D008565:Membrane Proteins; D012794:Sialic Acids; D017638:Asbestos, Crocidolite; D001194:Asbestos; D012822:Silicon Dioxide; D012964:Sodium; D009439:Neuraminidase; D011188:Potassium