Sh. Gavett et G. Oberdorster, CADMIUM CHLORIDE AND CADMIUM METALLOTHIONEIN-INDUCED PULMONARY INJURYAND RECRUITMENT OF POLYMORPHONUCLEAR LEUKOCYTES, Experimental lung research, 20(6), 1994, pp. 517-537
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.