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Biomedical subjects

V L Moore

Publications and source records attributed to V L Moore.

At least 19 recordsLinked to original sources

Pulmonary function in rabbits with BCG-induced lung disease.

This study was performed to determine whether the lung histological changes which occur in rabbits following intravenous injection of killed Bacilli Calmette-Guérin (BCG) are accompanied by measurable changes in pulmonary function. We measured pulmonary function in New Zealand white rabbits 3 weeks after intravenous injection of BCG and in normal rabbits. After a tracheostomy and carotid artery catheterization was performed, each anesthetized rabbit was placed in a body plethysmograph for pulmonary function testing. Following the measurements, the lungs were removed for weighing and histological evaluation. In the BCG-treated rabbits, the lung weight/body weight ratios were 152% greater, the pulmonary resistance was 104% higher, dynamic compliance was 45% lower, minute ventilation was 28% greater, and the delta AaPO2 gradient was 13 torr higher than in the normal control rabbits. Histological evaluation of the BCG-treated animals revealed diffuse pulmonary involvement with non-caseating granulomas.

Airway Resistance

An animal model of hypersensitivity pneumonitis in rabbits. Development of chronic pulmonary inflammation and cell-mediated hypersensitivity after repeated aerosol challenge.

Chronic pulmonary inflammation was produced in immunized rabbits by repeated aerosol exposure to soluble antigen. The pulmonary inflammatory response was correlated with the development of cell-mediated hypersensitivity in the lung as evaluated by migration-inhibition studies using bronchoalveolar cells. Such inflammation could be produced with either pigeon dropping extract, an etiologic agent of hypersensitivity pneumonitis, or with human gamma globulin. Development of the inflammatory response was immunospecific and could not be transferred to normal recipients with large quantities of immune serum. Collectively, these data suggest that the development of pulmonary inflammation was due to a cell-mediated immunologic reaction in the lung.

Aerosols

Immune complex disease in guinea pig lungs: elicitation with pigeon serum.

Immune complex- and T cell-mediated reactions to organic antigens appear to contribute to the pathogenesis of hypersensitivity pneumonitis in humans. Because pigeon serum is one of the reagents used by clinicians to diagnose this disease, we assessed its potential to elicit immune complex-mediated pulmonary inflammation in guinea pigs. Animals were immunized with different concentrations of pigeon serum protein emulsified in complete Freund's adjuvant, and serums were collected at 4-day intervals after the booster injection. The largest amounts of tissue-fixing (IgG1) and complement-fixing (IgG2) antibodies to pigeon serum were detected in guinea pigs immunized with 1.0 mg of pigeon serum protein 20 to 24 days after the secondary immunization. Therefore, the responses of these animals and of recipients of serum from these animals to aerosol challenge with either homologous (pigeon serum) or heterologous (bovine gamma globulin) immunogen was investigated. Actively and passively immunized guinea pigs developed pulmonary inflammation only after exposure to aerosolized pigeon serum. However, lesions were not observed in the lungs of complement-deficient recipients of immune serum that had inhaled homologous immunogen. These observations suggest that such pigeon serum-elicited pulmonary inflammation in guinea pigs is a manifestation of a complement-dependent, humoral-immune mechanism of pathogenesis and thus is consistent with an immune complex disease.

Allergens

Effect of hypersensitivity on protein uptake across the air-blood barrier of isolated rabbit lungs.

In previous studies with isolated perfused rabbit lungs, we observed that human serum albumin (HSA) and ovalbumin, introduced into the isolated lungs as an aerosol, entered the pulmonary circulation antigenically intact. The "inhaled" proteins were also broken down in the lung. When lungs from animals immunized with one protein inhaled the two proteins simultaneously, absorption of intact antigen was specifically reduced, and there was a nonspecific increase in the appearance of metabolites of both proteins in the blood. In the present study, we investigated the antigen-specific and nonspecific effects of two types of hypersensitivity responses on protein absorption across the air-blood barrier of isolated rabbit lungs. In one group of lungs, an acute hypersensitivity response was induced by introducing HSA into the blood perfusing lungs from HSA-immunized rabbits. In another, the rabbits had been previously exposed to chronic HSA aerosol until their lungs exhibited a chronic immunologic inflammatory response. Lungs from both groups were insufflated simultaneously with HSA, and a nonspecific protein, ovalbumin. Lungs in which the acute anaphylactic response was induced showed no alteration in the absorption of either intact protein compared with HSA-immunized controls, but absorbed a somewhat larger quantity of breakdown products of the specific antigen. Lungs undergoing the chronic alveolar inflammation were more permeable to nonspecific protein than were noninflamed lungs. Despite the increased permeability to nonspecific protein, the absorption of antigen was blocked as effectively as in immune but noninflamed controls. In these chronically inflamed lungs, the absorption of antigen breakdown products was enhanced. The results indicate that both immunologic and inflammatory mechanisms may control the amounts of inhaled soluble proteins that reach the blood via the alveolocapillary barrier. Alterations in the absorption of inhaled proteins and their metabolites across the air-blood barrier during certain types of hypersensitivity responses may be of immunologic and pathologic significance.

Absorption

Humoral and cellular immune responses in Aspergillus fumigatus pulmonary disease.

This study was designed to evaluate immunologic differences between aspergilloma (A) and allergic bronchopulmonary aspergillosis (ABPA), comparing the results to atopic and nonatopic control subjects. Humoral studies included skin tests with common inhalant antigens and Aspergillus fumigatus. Total and specific IgE and other immunologlobulin levels and serum precipitins were evaluated against A. fumigatus. Cellular immunity was studied with routine skin testing and phytohemaqglutinin-induced lymphocyte blast transformation. Antigen-induced blast transformation was also carried out with the use of serial dilutions of A. fumigatus. All patients with ABPA were atopic and had marked elevations of IgE. None of the patients were atopic and they had normal IgE levels. Immediate and late skin reactivity to A. fumigatus was low in control and A groups but high in 2 patients with ABPA. IgG antibody against A. fumigatus was generally greater in the ABPA group. Both ABPA and A had serum precipitating antibody against A. fumigatus. The atopic controls had elevated IgE levels and immediate skin test reactivity to A. fumigatus, and one also had weak serum precipitins against A. fumigatus. IgE antibody against A. fumigatus was generally higher in ABPA than A. ABPA and A patients had elevated stimulation indices (SI) to A. fumigatus. No stimulation could be detected with cells from control subjects. This study indicates that both T and B cell sensitization may play a role in the development of or as a response to aspergillus-related pulmonary disease.

Antibody Formation

Anaphylaxis in isolated rabbit lungs.

Lungs from rabbits sensitized to ovalbumin or bovine gamma-globulin were isolated and perfused with autologous blood. The response to antigen challenge via the perfusate was immunologically specific and characterized by a marked increase in perfusion resistance, a moderate increase in airway resistance and a small decrease in lung compliance. The response could also be elicited by specific antigen challenge in lungs from sensitized rabbits perfused with blood from normal rabbits and in lungs from normal rabbits perfused with blood or plasma from sensitized rabbits. The magnitude of the response was greater when blood or plasma from sensitized animals was used as the perfusate. Therefore, blood and/or plasma factors appear to be the major contributors to the response.

Airway Resistance

Cell-mediated immunity in the lungs of rabbits using conjugated proteins.

A study using direct macrophage migration inhibition of cells from the lower respiratory tract of rabbits immunized with conjugated proteins, incorporated into a killed BCG-oil emulsion, revealed that the reaction was largely carrier specific. The only exception was when bronchoalveolar cells (BAC) from animals immunized with dinitrophenol coupled to ovalbumin (DNP-OA) were significantly immobilized with DNP coupled to bovine gamma-globulin (BGG) in which the ratio of DNP/BGG was high [DNP-BGG(H)]. This result could not be explained by a toxic effect or by a high net negative charge on DNP-BGG(H). In addition, inhibition of BAC from DNP-OA-immunized rabbits was not observed when the ratio of DNP to BGG was reduced approximately 5-fold.

Animals

Absorption of inhaled antigen into the circulation of isolated lungs from normal and immunized rabbits.

The purpose of this study was to determine whether the absorption of inhaled antigen (Ag) across the pulmonary air-blood barrier of the isolated perfused lung can be modulated by immunologic mechanisms. Lungs from immunized or nonimmunized rabbits were removed, ventilated, and perfused with autochthonous blood. Radioiodinated Ag (human serum albumin or ovalbumin) was introduced as an aerosol into the isolated lung for 15 min and blood samples were taken over a 4-h period. The results showed that radioactivity fom inhaled Ag entered the perfusing blood as two fractions. One fraction was precipitable by 5% trichloroacetic acid or antiserum. The TCA-soluble fraction chromatographed differently from iodide and may have represented metabolites of the Ag. Immunization specifically reduced the amount of antigenically intact protein entering the blood. On the other hand, the metabolite reached higher concentrations in the blood of immunized lungs. We conclude that the alveolar capillary barrier of the normal rabbit lung could provide a significant route of entry for inhaled antigen into the systemic circulation and that immunization reduces absorption via this route and enhances pulmonary metabolism of the Ag.

Absorption

Immunologic block against antigen absorption from isolated perfused rabbit lungs.

In previous studies with isolated perfused rabbit lungs, we observed that inhaled human serum albumin (HSA) or ovalbumin (OA) entered the pulmonary circulation antigenically intact. The inhaled proteins were also metabolized in the lung. Immunization reduced the amount of intact protein and increased the amount of metabolites absorbed. In the present study, we have begun to characterize the immune mechanisms responsible for reduced antigen absorption. A humoral immune mechanism appeared to be involved because the phenomenon could be passively transferred to normal animals by administering immune serum either 18 hr or immediately before antigen inhalation. The reduction was also observed when lungs from immunized rabbits were perfused with normal rabbit blood, indicating that antibodies in both lung and blood may be involved. Experiments, in which lungs from immunized rabbits were simultaneously insufflated with the immunizing antigen and with a nonspecific protein, demonstrated that the block against antigen absorption was specific for the immunizing antigen and was not due to some antigen-induced nonspecific changes in lung physiology.

Absorption

Antigens in pigeon breeder's disease: the use of pigeon dropping antigens in detecting antibody activity.

Sera from patients with pigeon breeder's disease were analysed for precipitating antibodies by immunodiffusion and immunoelectrophoresis using whole pigeon dropping extract (PDE) and a purified fraction of PDE (PDE1) as antigens. For comparison, sera from asymptomatic pigeon breeders and normal individuals were also tested for precipitating antibodies. Whereas whole PDE formed precipitin lines with normal serum as well as with serum from symptomatic and asymptomatic pigeon breeders, PDE1 formed precipitin lines only with serum from individuals exposed to pigeons, This suggests that whole PDE forms non-specific (non-antigen-antibody reactions) as well as specific precipitin lines, while PDE1 appears to form only specific lines. These data indicate that whole PDE has limited usefulness in studies of pigeon breeder's disease. It is also possible that PDE1 will be useful in studies of this disease.

Alveolitis, Extrinsic Allergic