title: Cadmium chloride and cadmium metallothionein-induced pulmonary injury and recruitment of polymorphonuclear leukocytes.
abstract: Pulmonary exposure of rats to either cadmium chloride (CdCl2) or cadmium 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 damage to the pulmonary epithelium. The purpose of this study was to investigate mechanisms of PMN recruitment following exposure to these forms of cadmium. Fischer 344 rats were intratracheally instilled with 10 micrograms cadmium in the form of CdCl2 or CdMT, and the time course of pulmonary inflammation and PMN migration activity was determined. PMN numbers, permeability, and PMN migration activity of lung lavage supernatant 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 1 day when permeability had increased to a small but significant degree. Elastase-modified forms of alpha-1-proteinase inhibitor (alpha 1PI), with molecular weights of 80 and 51 kd, have been reported to be highly chemotactic for PMNs. Antiserum to alpha 1PI significantly inhibited PMN migration activity detected in supernatants 1 day after exposure to either CdCl2 or CdMT. The results suggest that both CdCl2 and CdMT induce the formation of high molecular weight modified forms of alpha 1PI in the airways; these factors may traverse damaged epithelium to recruit PMNs from the vasculature. Additional small or lipophilic factors, undetectable by the methods of this study, may be responsible for the early influx of PMNs following CdMT exposure in the absence of increased epithelial permeability.
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine, New York.
authors.forename: S H
authors.initials: SH
authors.lastname: Gavett
authors.forename: G
authors.initials: G
authors.lastname: Oberdörster
mesh_terms: D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D055370:Lung Injury; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013481:Superoxides / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis
chemical_list: D002712:Chlorides; D000515:alpha 1-Antitrypsin; C004203:cadmium-binding protein; D002104:Cadmium; D013481:Superoxides; D008668:Metallothionein; D019256:Cadmium Chloride