Changes in glycerophosphatides and their ether analogs in lung lavage of rabbits exposed to nickel dust.

In rabbits exposed for 3 and 6 months to 1 mg/m3 of metallic nickel dust, the increase of pulmonary phospholipids was about 3 and 4 times, respectively. The corresponding increase of phospholipids in lung lavage was about 6 and 11 times, respectively. A detailed study of the phospholipid composition in lung lavage from the rabbits exposed for 3 months showed an increased amount of nonacidic phospholipids and a decreased amount of phosphatidylglycerols. Although most of the increase was due to the disaturated phosphatidylcholines, the relative increase was highest for the ether analogs of phosphatidylethanolamines. In the exposed rabbits the two ether analogs, 1-alk-1'-enyl-2-acyl- and 1-alkyl-2-acyl-sn-glycero-3-phosphoethanolamines, constituted 10.4 and 8.2%, respectively, of the phosphatidylethanolamine fraction. The corresponding values in the control rabbits were 5.2 and 0%, respectively. The occurrence of 1-alkyl-2-acyl-sn-glycero-3-phosphoethanolamines and the increase of 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoenthanolamines indicate that the biosynthetic synthetic pathway of ether lipids may be stimulated in the exposed rabbits. This is of interest since a high proportion of ether lipids is observed in many tumors and since some nickel compounds may give respiratory tumors.

Toxicology of nickel.

Rabbits were exposed to low levels of airborne metals for 1-8 months, 5 days/week, 6 hours/day. After exposure, lung tissue was examined by light and electron microscopy. Macrophages lavaged from the left lung were examined morphologically and functionally. Phospholipids were analysed in lung tissue or lavage fluid. Metallic nickel dust, 0.1-1 mg/m3, affected alveolar macrophages, alveolar epithelial type II cells and phospholipids. In the lung tissue, nodular accumulation of macrophages was seen, and the volume density of alveolar type II cells was elevated. The amount of phospholipids was markedly increased, mainly due to an increase in disaturated phosphatidylcholines. After 1 month of exposure the macrophages appeared active. After 3 months they appeared 'overfed' and inactive. Metallic iron, chromium and cobalt did not produce the same effects as nickel. Exposure to 0.2 mg/m3 soluble nickel as nickel chloride produced almost identical effects to those of metallic nickel, indicating that the effect of the metallic nickel particles was caused by nickel ions. Exposure to cadmium chloride produced nearly all the effects produced by nickel chloride. However, cadmium chloride increased the level of lysozyme in the macrophages whereas nickel chloride decreased it. Cadmium chloride also produced interstitial alveolitis and cytoplasmic blebs on the surface of the macrophages. Cobalt chloride affected the growth of the type II cells, which formed nodules, but did not seem to affect the production of surfactant material by those cells. Copper chloride produced no effect apart from a slight increase in volume density of the type II cells. Thus, of four divalent metal ions, three (Ni2+, Cd2+ and Co2+) in similar concentrations in the inhaled air produced clear but different pathological effects in the lungs.