Inhaled particles such as asbestos and silica are toxic to pulmonary cells. Our hypothesis is that non-specific (i.e., non-receptor mediated) binding and subsequent uptake of positively-charged particles are mediated by negatively-charged cell surface sialic acid groups. In support of this hypothesis, we have shown that chrysotile asbestos causes damage to erythrocyte membranes through binding to terminal sialic acid (SA) residues. The hemolytic events involved (1) binding of the positively-charged chrysotile fibers to negatively-charged SA groups, (2) rapid (within 5 min) distortion of the cells, (3) redistribution of SA groups, and (4) alterations of intracellular Na+, K+ ratios. Negatively-charged crocidolite asbestos bound to and distorted red cells but had no effect on SA groups or ion flux. To establish whether or not similar mechanisms of membrane injury play a role in particle-induced toxicity of pulmonary cells, we have extended our studies to pulmonary macrophages and have shown the following: (1) Wheat germ agglutinin (WGA), a lectin which binds to sialic acid, is distributed evenly across macrophage surfaces. (2) Positively-charged carbonyl iron (Fe) spheres and chrysotile asbestos fibers bind to macrophage membranes at 4 degrees C and the binding is blocked by a dose-dependent pretreatment of the cells with WGA. Other lectins such as Ricin and ConA do not inhibit binding at comparable doses. (3) Fe-spheres normally are readily phagocytized by macrophages at 37 degrees C. In the presence of WGA, over 90% of the phagocytic activity is blocked, but other lectins have no effect. These studies support our hypothesis that charged surface sialic acid groups play a role in particle binding and phagocytosis. In addition, ongoing studies have shown that particles induce the production of arachidonic acid metabolites by pulmonary macrophages. Induction of these potent mediators of inflammation is stimulated through interactions between terminal sialic acid groups and particles bound to the macrophage membranes.
