CADMIUM CHLORIDE AND CADMIUM METALLOTHIONEIN-INDUCED PULMONARY INJURYAND RECRUITMENT OF POLYMORPHONUCLEAR LEUKOCYTES

Pulmonary exposure of rats to either cadmium chloride (CdCl2) or cadmi um metallothionein (CdMT) was previously reported to induce an influx of polymorphonuclear leukocytes (PMNs) to the airways, but only CdCl2 caused a significant increase in lung permeability, indicative of dama ge to the pulmonary epithelium. The purpose of this study was to inves tigate mechanisms of PMN recruitment following exposure to these forms of cadmium. Fischer 344 rats were intratracheally instilled with 10 m u g cadmium in the form of CdCl2, or CdMT, and the time course of pulm onary inflammation and PMN migration activity was determined PMN numbe rs, permeability, and PMN migration activity of lung lavage supernatan t peaked 1 to 2 days after CdCl2 exposure. PMN migration activity was not detected 5 h after CdMT exposure, despite a peak of PMN numbers 10 h after exposure, but was increased by 2 day when permeability had in creased to a small but significant degree. Elastase-modified forms of alpha-1-proteinase inhibitor (alpha(1)PI), with molecular weights of 8 0 and 51 kd, have been reported to be highly chemotactic for PMNs. Ant iserum to alpha(1)PI significantly inhibited PMN migration activity de tected in supernatants 2 day after exposure to either CdCl2 or CdMT. T he results suggest that both CdCl2 and CdMT induce the formation of hi gh molecular weight modified forms of alpha(1)PI in the airways; these factors may traverse damaged epithelium to recruit PMNs from the vasc ulature. Additional small or lipophilic factors, undetectable by the m ethods of this study, may be responsible for the early influx of PMNs following CdMT exposure in the absence of increased epithelial permeab ility.