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Biomedical subjects

K J Johnson

Publications and source records attributed to K J Johnson.

At least 199 records · Page 11Linked to original sources
PubMed1982

Acute and progressive lung injury after contact with phorbol myristate acetate.

Because of its potent ability to activate leukocytes and macrophages, resulting in the generation of large amounts of oxygen products (O-2, H2O2), phorbol myristate acetate (PMA) has been instilled into the air-ways of rats. The resulting acute lung injury is dose-dependent on the amount of PMA employed, is chiefly confined anatomically to the alveolar and interstitial compartments, is neutrophil-independent, and can be inhibited by catalase but not by superoxide dismutase. These data suggest that the generation of H2O2 is major mechanism involved in this method of acute lung injury. It has also been demonstrated that a progressive pattern of lung injury develops after exposure to PMA, with the onset of an interstitial fibrotic reaction by the sixth day. These data reinforce our recent studies, in which both acute and progressive injury occurs in lungs of rats when H2O2 is generated.

Acute Disease↗
PubMed1981

In vivo damage of rat lungs by oxygen metabolites.

The intrapulmonary instillation into rat lung of enzymes that generate oxygen metabolites results in acute lung injury. The injection of xanthine oxidase and xanthine produces acute lung injury that, in the presence of superoxide dismutase, but not in the presence of catalase, can be significantly diminished, suggesting that O2- has the capacity to injure the lung. Instillation of a generator of H2O2, namely glucose oxidase, will, in sufficient quantities, produce acute injury that is not neutrophil-dependent. When either a low dose of glucose oxidase alone or lactoperoxidase alone is employed, little lung injury occurs. However, instilling the combination of the two enzymes produces severe, acute injury that can be blocked in a dose-dependent manner by catalase, but not by superoxide dismutase. Purified human leukocytic myeloperoxidase, but not horseradish peroxidase, will substitute for lactoperoxidase in the model of lung injury. The lung damaging effects of these enzymes cannot be attributed to the presence of contaminating proteases. Acute lung injury produced by the instillation of glucose oxidase and lactoperioxidase progresses to interstitial fibrosis. These studies represent a direct application of generators of oxygen metabolites to the in vivo induction of lung injury. The data suggest that rat lung is susceptible to injury by a variety of oxygen metabolites, including O2-, H2O2 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.

Animals↗
PubMed1981

Substrate hydrolysis by immune complex-activated neutrophils: effect of physical presentation of complexes and protease inhibitors.

The ability of rat leukocytes to hydrolyze a radiolabeled, surface-bound protein substrate in a solid phase assay was determined, and various factors that influence the process were measured. Unstimulated leukocytes hydrolyzed very little substrate. When the cell suspension was mixed with zymosan particles or incubated with preformed immune complexes, the amount of substrate hydrolysis increased dramatically. Not surprisingly, immune complexes at equivalence proved to be the most effective in eliciting the response. Immune complexes attached to the surface along with the protein substrate were able to effectively induce hydrolysis, though they were not as effective as immune complexes in suspension. Three protease inhibitors, alpha 1-antitrypsin, alpha 2-macroglobulin, and soybean trypsin inhibitor, which were able to neutralize nearly all of the protease activity in rat neutrophil lysates, were tested for their ability to inhibit immune complex-induced protein hydrolysis. It was found that when the inhibitors were surface bound along with the substrate protein, they were effective in preventing the neutrophils from hydrolyzing the protein. However, when the same inhibitors were present in the fluid phase, they were much less effective. The relative ineffectiveness of fluid phase protease inhibitors to block the protease activity of contact-activated leukocytes may explain how immune complex injury can take place in the presence of high concentrations of serum inhibitors.

Animals↗
PubMed1981

Suppression by superoxide dismutase of immune-complex--induced pulmonary alveolitis and dermal inflammation.

The possible role of oxygen metabolic products in immune-complex--induced injury of rat lung and of dermal blood vessels has been probed with the use of two inhibitors, superoxide dismutase (SOD) and catalase. With the use of the reversed passive Arthus reaction in the skin, local administration of SOD, but not of catalase, blocked the early phase of the tissue injury, as quantitated by the leakage of homologous albumin. The early phases of immune-complex--induced injury of the lung were completely blocked by the parenteral (intraperitoneal) administration of SOD. Except at very high doses, SOD did not interfere with chemotactic-factor--induced release of lysosomal enzymes from rat neutrophils. These data suggest that oxygen metabolic products such as O(2-) may play an important role in the early phases of damage produced in rat alveolar walls and dermal vasculature by the deposition of immune complexes.

Animals↗
PubMed1980

A study of the origin of pulmonary macrophages using the Chédiak-Higashi marker.

Using bone marrow reconstitution techniques with cells bearing the Chédiak-Higashi marker, the authors have been able to demonstrate in mice that both interstitial and intraalveolar macrophages of the lung are derived from bone marrow precursor cells. The morphologic approach (transmission electron microscopy) employed in this study provides direct evidence and confirmation of earlier reports, in which entirely different techniques were used to study cell traffic in the lung. The use of the Chédiak-Higashi marker has great advantages over other more cumbersome and difficult techniques.

Animals↗
PubMed1979

Immunologic vasculitis in beige mice with deficiency of leukocytic neutral protease.

Immune complex vasculitis has been induced in normal mice and in mice with features of the Chediak-Higashi syndrome ("beige" mice). The accumulation of neutrophils in peritoneal exudates after the injection of C5a is not quantitatively depressed in beige as compared with normal mice. Immune complex-induced vasculitis in these two strains of mice is not quantitatively different, as assessed by vascular damage (vasopermeability changes and histologic criteria). Measurements of leukocyte enzymes confirm the findings of Vassalli et al. that leukocytes of beige mice lack neutral protease activity. The data suggest that the neutral protease of murine leukocytes does not account for the vascular damage of immune complex vasculitis.

Animals↗
PubMed1977

Suppression of immune complex-induced inflammation by the chemotactic factor inactivator.

Small amounts (10(-10) mol) of purified human chemotactic factor inactivator (CFI) suppress leukocytic infiltration, permeability changes, and hemorrhage associated with acute immune complex-induced injury in rats. The reversed passive dermal Arthus reaction and acute immune complex-induced alveolitis in rats have served as the model systems of inflammation. The mechanism of inhibition does not appear to relate to interference with formation and deposition of immune complexes, or with fixation of complement in vitro or iv vivo. Human CFI inhibits in vitro the chemotactic activity generated in complement-activated rat serum. The inhibitory effects of human CFI are not seen if it is first heat inactivated. The data provide the first direct support for the conclusion that CFI has anti-inflammatory activity.

Aminopeptidases↗
PubMed1977

Regulatory dysfunction in leukotaxis.

The chemotactic factor inactivator (CFI) in human serum appears to have important regulatory function in the inflammatory response. In humans with elevated serum levels of CFI, defective mobilization of leukocytes in vivo has been noted, both in skin windows and in skin testing with various antigens. In experimental immune complex-induced acute inflammatory reactions in rat skin and lung, purified human CFI at very low doses has potent antiinflammatory effects and is able to suppress permeability changes, neutrophil infiltration, and hemorrhage, all of which are dependent initially on the role of leukotactic mediators.

Animals↗
PubMed1977

Isolation from human serum of an inactivator of bacterial lipopolysaccharide.

By a series of chromatographic procedures involving precipitation by salt, gel filtration, anionic exchange, and hydroxyapatite elution, a protein--termed the lipopolysaccharide inactivator (LPS-I)--has been isolated from normal human serum. As a result of treatment of bacterial lipopolysaccharide (LPS) by LPS-I, the treated LPS loses its toxicity for mice and reactivity in the Limulus assay and appears to be irreversibly disaggregated. The inactivation of the LPS by the purified LPS-I is temperature and time dependent and is not blocked by the addition of irreversible inhibitors of serine esterases. The LPS inactivator migrates as an alpha-globulin in whole serum and has a sedimentation velocity of approximately 4.5S. Characteristics of the inactivated LPS are briefly described using internally labeled LPS.

Alpha-Globulins↗
PubMed1974

Acute immunologic pulmonary alveolitis.

Acute immunologic injury of rat lung has been induced by the intrabronchial injection of heterologous antibody and the intravenous injection of radiolabeled antigen. Within 4 h an acute hemorrhagic neutrophil-rich exudate develops in alveolar and interstitial areas and then gradually fades. Lung injury in this model can be quantitated by measurements of increased vascular permeability and extractable hemoglobin. By the use of immunofluorescent techniques, alveolar and interstitial deposits of antigen and antibody have been demonstrated, but not the third component of complement (C3). Although not found in relation to immune complexes, C3 is nevertheless present in damaged lung as measured by accumulation of radiolabeled C3 from the circulation. Ablation experiments indicate the requirement for both circulating neutrophils and C3 for the development of lung injury. These studies provide definition for the development of lung damage induced by immune complexes.

Animals↗