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V V Damiano

Publications and source records attributed to V V Damiano.

10 recordsLinked to original sources
PubMed1991

Induction of unilateral pulmonary fibrosis in the rat by cadmium chloride.

Intralobar instillation of cadmium chloride (CdCl2) into the left lungs of rats initiated a sequence of events that culminated in massive unilateral intraluminal fibrosis. Early events (days 1 and 2) after CdCl2 administration included infiltration of the treated lung with polymorphonuclear leukocytes, an increase in the number of alveolar macrophages, activation of the macrophages as assessed by the induction of cathepsin L mRNA, and the induction in liver of mRNA for the acute-phase response protein, alpha 1-acid glycoprotein. By days 5 to 7 in the treated lungs, mRNA for procollagen alpha 1(I) increased 20- to 60-fold, and mRNA for procollagen alpha 1(III) increased 4- to 14-fold. These increases were correlated with the almost complete filling of the alveolar spaces with fibroblasts and collagen. The contralateral lung exhibited no significant change in histology but showed a similar induction of collagen gene expression. These increases were tissue-specific, as the livers of these animals showed no change from the control levels of collagen gene expression. Procollagen messages in the treated and contralateral lungs were equally competent for translation into pro-alpha 1(I) and pro-alpha 2(I) polypeptides. Both the treated and contralateral lungs increased hydroxyproline content about 1.5- to 2-fold over 14 days. The contralateral lung, but not the treated lung, showed a 2-fold increase in lung volume. As a result, the collagen density (mg collagen/ml lung volume) doubled in the treated lung but remained constant in the contralateral lung. These data indicate that CdCl2 caused a rapid induction of pulmonary fibrosis in the treated lungs of rats and stimulated histologically normal growth of the contralateral lung.

Actins↗
PubMed1990

Intraluminal fibrosis induced unilaterally by lobar instillation of CdCl2 into the rat lung.

Lung injury induced by intratracheal instillation of cadmium chloride (CdCl2) into the rat lung may serve as a model of human interstitial lung disease. In this study, CdCl2 solutions were instilled through a lobar bronchus into the left lung of the rat. Two doses (400 micrograms or 50 micrograms of CdCl2, each in 400 microliters of neutral saline) were used and the morphologic changes occurring during the first 7 days after a single exposure were documented by light and electron microscopy. With the higher dose, inflammatory cells appeared in the alveolar interstitium 1 day after CdCl2 administration. Edema and thickening of the alveolar walls were evident, as were damaged type I epithelial cells and denuded basement membranes. Fibrin was found in the air spaces. Within 2 days, inflammatory cells were seen in large numbers and fibroblasts were observed passing through gaps in the alveolar basement membranes into the air spaces. By 4 and 7 days after CdCl2, various forms of intraluminal fibrosis, including intrabronchiolar budding, mural incorporation, and obliterative changes, were observed. The contralateral lungs had normal-appearing architecture for all the time points investigated. In the lower dose exposure, gradients of alveolar damage were observed in which normal lung, interstitial fibrosis, and/or intraluminal fibrosis were seen within treated lungs. In the mildly damaged regions, interstitial fibrosis predominated, while in the more severely damaged regions, mural incorporation of the convoluted basement membranes was observed. The pulmonary fibrosis that developed appeared to be similar to some human interstitial lung diseases and may offer a system in which to study the regulation of collagen deposition and fibrosis development in these pathologic conditions.

Animals↗
PubMed1988

Ultrastructural quantitation of peroxidase- and elastase-containing granules in human neutrophils.

Previous ultrastructural studies of human neutrophils showed two distinctive granule types, the azurophil (peroxidase-positive) and the specific (peroxidase-negative). By identification of granules with peroxidase activity and those immunopositive for elastase antigen, the authors defined two subpopulations of azurophil granules, one that contained peroxidase activity and no measurable elastase antigen and another that contained elastase antigen associated with a small amount of peroxidase activity. They quantitated the peroxidase-positive as well as the elastase-positive granules in human peripheral blood neutrophils and found an average of 1536 +/- 69 peroxidase-positive granules per neutrophil. Of these, 399 +/- 20 were also elastase-positive. The average elastase concentration per neutrophil was 1.59 pg, and the average concentration per granule was 4 X 10(-3) pg. It is concluded that in normal individuals approximately one-third of the azurophil granules contain elastase antigen. Because neutrophil elastase has been implicated in the pathogenesis of emphysema, quantitation of its distribution within the cell presents an approach that may help define selective azurophil granule release and its relationship to the development of emphysema.

Cytoplasmic Granules↗
PubMed1986

Immunolocalization of elastase in human emphysematous lungs.

The current working hypothesis concerning the pathogenesis of human pulmonary emphysema proposes that neutrophils migrate through the alveolar interstitium and degranulate, releasing proteolytic enzymes into the interstitium. These enzymes, in particular elastase, can bind to and degrade interstitial elastin. This report describes an immunohistochemical, ultrastructural technique that utilizes polyclonal antibodies to localize neutrophil elastase in human lungs. Using both the immunoperoxidase and the immunogold methods on thin, embedded sections of surgically resected human emphysematous lung tissue, elastase was localized in neutrophils in the lung interstitium and extracellularly in association with interstitial elastic fibers in human lungs that showed local emphysema of varying severity. Quantitative morphometric data were obtained from the lungs of eight patients undergoing lobectomy for removal of pulmonary carcinomas. Patients had preoperative forced expiratory volume (FEV1)% levels ranging from 55 to 77. There was a correlation between a quantitative measure of the local distribution of neutrophil elastase in contact with alveolar interstitial elastin and the local presence of emphysematous change as determined by mean linear intercept of the various histologic sections. These data support the validity of the "protease-protease inhibitor balance hypothesis" as an explanation of the pathogenesis of human pulmonary emphysema.

Adult↗
PubMed1982

Neurtrophil degranulation in cadmium-chloride-induced acute lung inflammation.

Lobar intrabronchial instillation of cadmium chloride (200 micrograms/ml) in saline causes a reproducible acute pulmonary inflammation in dogs. The influx of inflammatory neutrophils from the circulation into the alveolar spaces reaches a maximum approximately 16 hours after the cadmium chloride treatment in the treated lobe, while the controlateral lung appears normal. Morphometric quantitation of peroxidase-positive (azurophilic) granules in the inflammatory neutrophils shows a 74% loss of these granules, with little or no loss of the peroxidase-negative (specific) granules. These data are in good agreement with the measured loss of intracellular elastase, an enzyme known to be localized in the azurophilic granules. The results suggest that degranulation of azurophilic granules may occur selectively during this chemically induced acute inflammation.

Animals↗
PubMed1981

A model of decreased functional alpha-1-proteinase inhibitor. Pulmonary pathology of dogs exposed to chloramine T.

The objective of this study was to develop an animal model representative of chronic human alpha-1-proteinase inhibitor deficiency. Eight dogs were treated with a mild oxidizing agent, chloramine T, with varying regimens for 3--27 wk. The capacity of the serum to inhibit both trypsin and elastase was examined and found to respond differently. Although immunologically determined levels of protease inhibitor did not change, the ability of serum to inhibit elastase in an in vitro assay decreased in direct response to chloramine T treatment. The trypsin inhibitory capacity was less affected. Emphysemalike alterations in lung morphology were observable when histologic sections were evaluated both subjectively and objectively by mean linear intercept measurements. The data suggest that this model parallels the emphysema associated with the genetic alpha-1-proteinase inhibitor deficiency in man.

Animals↗
PubMed1980

A morphologic study of the influx of neutrophils into dog lung alveoli after lavage with sterile saline.

The appearance of neutrophils in the alveoli of the lung is a common result of pulmonary infection, although the route of neutrophil migration across the alveolar wall has not been demonstrated in normal animals. Recently, however, several methods of stimulating the influx of neutrophils into alveoli have been developed. In the present study, the lung wash model was used to attract large numbers of neutrophils into the airways in order to identify the site of influx of alveolar neutrophils. The combined use of scanning and transmission electron microscopy has made it possible to visualize the migration of neutrophils from the capillaries, through the interstitial spaces, and through the epithelium at the junctions between Type I and Type II cells.

Animals↗
PubMed1979

Immunologic localization of elastin by electron microscopy.

Research on the pathogenesis of experimental emphysema has involved studies of the distribution of and destruction of elastin in the alveolar interstitium. The ill-defined organization of elastin in the alveolar interstitium makes it difficult to identify the elastin specifically by staining procedures ordinarily used for electron microscopy. This problem becomes more significant when the elastic tissue is fragmented during emphysema development and localization of the elastin fragments is essential. Therefore, a specific technique using high-titer antibodies against purified canine lung elastin was developed. The primary antibody was used on preembedded or etched postembedded sections. Localization of the antielastin IgG was accomplished with ferritin-labeled rabbit antisheep IgG as the secondary antibody. Treatment with the preimmune serum gave negligible ferritin background staining. The antielastin antibody did not react with lung connective tissue proteins such as the microfibrillar component of elastin or collagen or proteoglycan. The antielastin antibody appeared to be species specific. The method may be useful for studies of experimental emphysema.

Animals↗