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Biomedical subjects

D E Bice

Publications and source records attributed to D E Bice.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effects of inhaled nitrogen dioxide and diesel exhaust on developing lung.

This study examined age-related differences in the physiological responses of rats to inhaled automotive emissions. Previous reports suggested that lung development of animals exposed to oxidant gases early in life might be impaired, or that developing lungs might be more susceptible than adult lungs to inhaled toxicants. There were no previous comparisons in developing and adult lungs of the effects of atmospheres containing particles. The hypothesis tested in this study was that rats exposed to chronically inhaled nitrogen dioxide (NO2) or diesel exhaust during lung development were more susceptible to lung injury than rats that were exposed to these atmospheres as adults. Rats were exposed either throughout the period of lung development or as adults, and health effects in the two groups were compared at the end of exposure. Rats were exposed seven hours per day, five days per week for six months to NO2 at 9.5 ppm, to whole diesel exhaust diluted to a soot concentration of 3.5 mg/m3, or to filtered air as controls. These concentrations were selected to produce mild effects in adults. The younger group (developing) was conceived in the exposure atmospheres and exposed during gestation and through the age of six months, and the older group (adult) was exposed between six and twelve months of age. Health effects were evaluated at the end of six months' exposure and some measurements were repeated six months after the cessation of exposure. Measurements included respiratory function, pulmonary immune responses, lung clearance of radiolabeled particles, airway fluid enzymes, protein and cytology, lung tissue collagen and proteinases, lung burdens of diesel soot, lung morphometry and histopathology. Nitrogen dioxide slightly reduced body weight and altered airway fluid enzymes of both age groups, with a greater number of statistically significant differences detectable in the enzyme levels of animals exposed as adults. Normal lung development, as reflected in the size and functional efficiency at adulthood, was not affected by NO2 in this study. Diesel exhaust altered the airway fluid constituents as well as lung tissue collagen and proteinases of both age groups. Particularly striking was an almost sixfold increase in the percentage of neutrophils, a class of highly phagocytic leukocytes, in the airway fluids of adults after six months of exposure. Exhaust-exposed adults had increased numbers of cells in pulmonary lymph nodes, delayed clearance of both diesel soot and 134Cs-labeled particles, and increased lung weight. These changes did not occur in the rats exposed during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMed1986

Comparison of cell-mediated and humoral immunity in the dog lung after localized lung immunization.

This study evaluated cell-mediated immunity (CMI) and antibody production serially in control and immunized lung lobes of beagle dogs. A fiberoptic bronchoscope was used to immunize selected airways in the left cardiac lung lobe with 10(10) sheep red blood cells (SRBC); the right cardiac lobe received saline as control. The immune responses produced by this localized lung immunization were evaluated in cells and fluids obtained from blood and serial bronchial washings of the immunized and control lung lobes from 5 to 21 days after immunization. The antigen-specific production of procoagulant activity (LPCA) and inhibition of migration of alveolar macrophages by SRBC antigen were used to measure CMI in lavage cells from immunized and control lung lobes. The level of specific IgM and IgG antibody in lavage fluid from the control and immunized lung lobes was evaluated with the enzyme-linked immunosorbent assay (ELISA). The results of this study showed a significantly greater percentage of neutrophils and lymphocytes in the lavage fluid from the immunized lung lobes than from the control lung lobes. The increased number of lymphocytes in the immunized lung lobes showed a positive correlation with increased antibody concentrations. In contrast to the antibody response, CMI as measured by LPCA and MIF assays was positive, with nearly equal responses in control and immunized lung lobes. Even though there were only a few lymphocytes in the control lung lobes, there were apparently enough specific immune lymphocytes present that produced mediators after antigen stimulation to result in positive CMI responses.

Animals↗
PubMed1986

Enumeration of lymphocyte subpopulations in bronchoalveolar lavage of monkeys using an immunoenzymatic staining technique.

Percentages of T-helper (OKT4), T-suppressor (OKTB), and B (B1) lymphocytes were determined in peripheral blood and bronchoalveolar lavage (BAL) from six cynomolgus monkeys using an alkaline phosphatase based immunoenzymatic staining technique. The percent of each lymphocyte subset in lung lavage fluids were 40 +/- 9%, 26 +/- 7% and 11 +/- 4% for OKT4, OKT8 and B1, respectively. This cell distribution is similar to that obtained from normal human BAL samples using fluorescence techniques to evaluate binding. Values for peripheral blood lymphocyte subsets were not statistically different from BAL. This immunoenzymatic technique avoids the necessity for cell separation procedures which are used to alleviate problems with alveolar macrophage autofluorescence that can be encountered in fluorescence based assays of BAL samples. This technique also can be used by laboratories interested in lymphocyte characterization, but not equipped for fluorescence microscopy or flow cytometry.

Animals↗
PubMed1985

The role of macrophages in particle translocation from lungs to lymph nodes.

Red fluorescent and green fluorescent microspheres were instilled into separate but adjacent areas of dog lung lobes. After 7 days, the tracheobronchial lymph nodes that drained both of the instilled areas contained many macrophages with all red or all green microspheres but rarely both. This indicates that the particles did not translocate passively and that lung macrophages phagocytized the microspheres in the lung and carried them to the tracheobronchial lymph nodes. In addition, two populations of pulmonary alveolar macrophages (PAM's), one that had phagocytized red microspheres in vivo and one that had phagocytized green microspheres, were lavaged from the lungs of dogs, mixed into one population, and instilled back into a previously unexposed lung lobe of the same dogs. As in the first experiment, the tracheobronchial lymph nodes that drained the instilled area contained numerous macrophages with either all red or all green microspheres. This suggested that the instilled PAM's had migrated to the tracheobronchial lymph nodes. Thus, lung macrophages, including PAM's probably play a critical role in the induction of lung immunity and in protection from disease by determining particle translocation.

Animals↗
PubMed1985

The effect of local antibody responses on in vivo and in vitro phagocytosis by pulmonary alveolar macrophages.

This study used both in vitro and in vivo techniques to determine if local antigen deposition in the lung has a localized effect on immune phagocytosis by pulmonary alveolar macrophages (PAM). Using a fiberoptic bronchoscope, dogs were immunized in the left cardiac and left diaphragmatic lobes with sheep red blood cells (sRBC). The right cardiac and right diaphragmatic lobes of the same animals received saline as controls. Unimmunized dogs served as additional controls. On days 2, 6, 9, 13, and 16 after immunization, the left and right diaphragmatic lobes were lavaged, and the cells and fluids were analyzed in vitro. Opsonizing antibody in lavage fluids was first detectable at 6 days, peaked at 9-13 days, and was significantly higher in the immunized lobe than in the control lobe. Phagocytosis of sRBC caused by cytophilic antibody on PAM also peaked at 9 to 13 days. Significantly more cytophilic antibody activity was detected on day 9 in the immunized lobes, than in the control lobes. In vivo phagocytosis of sRBC was evaluated in the alveoli of immunized and control lobes of immunized dogs and a control lobe of unimmunized dogs. Phagocytosis of sRBC by PAM in the immunized lobes was about four times greater than that of the control lobes and about 40 times greater than that of a control lobe of an unimmunized dog. These results indicate that the local deposition of a particulate antigen in the lung had a localized effect on immune phagocytosis. These data suggest that the accumulation of antibody-secreting cells in the alveolus may play a critical role in pulmonary defense mechanisms.

Animals↗
PubMed1985

Effects of inhaled diesel exhaust on immune responses after lung immunization.

The inhalation of diesel exhaust particles and the accumulation of these particles in the lung-associated lymph nodes could alter the development of immune responses after lung immunization. To study this possibility, Fischer 344 rats and CD-1 mice were exposed to three levels of diesel exhaust (nominal concentration--7000, 3500, or 350 micrograms particles/m3). Chamber controls and exposed animals were immunized by intratracheal instillation of sheep red blood cells (SRBC) after 6, 12, 18, and 24 months of exposure. The number of anti-SRBC IgM antibody-forming cells (AFC) in the lung-associated lymph nodes and spleen was evaluated after immunization. The lung-associated lymph nodes from rats and mice exposed to the high levels of diesel exhaust were black with accumulated diesel particles, and the number of lymphoid cells was significantly elevated at each sacrifice time, while rats exposed to the medium level of diesel exhaust also had elevated numbers of cells in these tissues at 12, 18, and 24 months of exposure. The total number of AFC in the lung-associated lymph nodes was significantly elevated (p less than 0.05) in rats exposed to medium and high levels of diesel exhaust, but no significant effects were observed in exposed mice. Data expressed as AFC/10(6) lymphoid cells in rats and mice, and the level of specific IgM, IgG, or IgA antibody in rat sera were not significantly altered. We conclude that the increased cellularity, and the presence of diesel particles in the lung-associated lymph nodes, had a minimal effect on the immune and antigen filtration functions of these tissues.

Animals↗
PubMed1985

Local pulmonary immune responsiveness after multiple antigenic exposures in the cynomolgus monkey.

Two cynomolgus monkeys were immunized with sheep red blood cells in the right diaphragmatic lobe (RD) 4 times, 20 days apart. At the time of the fourth immunization, the left diaphragmatic lobe (LD) was also immunized. There were increases in both IgM anti-SRBC antibody-forming cells (AFC) and specific IgG in the RD lobe after each successive challenge. In the fourth challenge, the RD had an increase in anti-SRBC AFC 10-fold that of the LD lobe. The concentration of specific IgG was also higher in the RD lobe. With total protein as an indicator of vascular permeability, the LD had a greater increase in vascular permeability than did the RD. These data suggest that the increased immune responsiveness of the RD after multiple challenges was in part locally derived rather than entirely caused by increased recruitment of immune cells and antibody from the blood.

Animals↗
PubMed1985

Effect of age on antibody responses after lung immunization.

The effects of age on the number of lymphoid cells producing specific IgM antibody (AFC) and the level of specific IgM, IgG, and IgA antibody after lung immunization were evaluated in groups of dogs 2 through 16 yr of age. A trend for lowered antibody responses in blood was observed with increasing age, and significantly lowered antibody responses were measured in lavage fluids from immunized lung lobes of older dogs. Statistical evaluations indicated that the lowered antibody responses in the lung were due in part to the reduced AFC and level of specific antibody in the blood. However, a less intense inflammatory response to antigen instilled into the lungs of older dogs also significantly contributed to the lowered antibody responses in their lungs. Additional studies are needed to determine if the loss of inflammation and antibody responses in the lungs of aged dogs increases their susceptibility to pulmonary infections.

Aging↗
PubMed1985

Lung localization of antibody-forming cells stimulated in distant peripheral lymph nodes.

Previous studies have shown that antibody-forming cells (AFC) produced in the lung-associated lymph nodes after lung immunization enter the blood and are subsequently extravasated into immunized lung lobes. This study evaluated AFC in blood and lung lavage fluids following simultaneous stimulation of the thoracic and popliteal lymph nodes with two antigenically distinct immunogens. Five dogs were immunized in the hind feet with rabbit red blood cells (RRBC) and in the left cardiac lung lobe with sheep red blood cells (SRBC). The number of anti-SRBC and anti-RRBC AFC in the blood and lavage fluids was periodically evaluated. The results indicated that both immunizations significantly increased the number of AFC in the blood. The number of AFC to RRBC and SRBC antigens was significantly higher in the immunized lung lobes than in the control lung lobes. A comparison of the number of RRBC and SRBC AFC in the immunized or control lung lobes, relative to the number of RRBC and SRBC AFC in the blood, indicated that AFC to both antigens entered the lung at the same rate. We conclude that AFC produced in distant lymphoid tissues enter the lung from the blood as readily as AFC produced after lung immunization.

Animals↗
PubMed1983

Effects of acute nitrogen dioxide exposure on cellular immunity after lung immunization.

The effects of acute NO2 exposure on antigen-specific cell-mediated lung immunity in Fischer 344 rats were evaluated. Animals were exposed for 24 hr to either room air or 5, 10, or 26 ppm NO2 before intratracheal immunization with 10(8) sheep red blood cells (SRBC). Cellular immunity was evaluated by antigen-specific lymphocyte stimulation assays of pooled lymphoid cell suspensions from either the thoracic lymph nodes or spleens. Elevated cellular immunity was observed after exposure to NO2. The ability of the 26 ppm NO2 exposure to increase cellular immunity seemed to parallel, and in some cases even exceed, that seen in control animals immunized with SRBC mixed with 2 X 10(7) heat-killed Bacillus Calmette-Guerin. These results support the theory that lung damage, and/or alterations of regulatory populations of immune cells, induced by agents such as NO2 can be responsible for the production of abnormally elevated immune responses to antigens deposited in the damaged lung.

Animals↗
PubMed1983

Evaluation of the pulmonary immune response by analysis of bronchoalveolar fluids obtained by serial lung lavage.

Lavage fluids were obtained from Beagle dogs by serial bronchoalveolar lavage from immunized and control lung lobes 3-21 days after local deposition of sheep red blood cells. Results showed that immunized lobes contained more total protein, albumin, IgG and antigen-specific antibody than did unimmunized control lobes or lobes that received autologous red cells in saline. Antigen-specific antibody was present in the lavage fluid from 7 through 21 days after immunization. Mercaptoethanol treatment of lavage fluid had little effect on the antibody titer, suggesting that IgG, and possibly IgA, were the predominant immunoglobulin classes in the antigen-specific antibody pool throughout the course of the serial lavage study. The data suggest that most of the antigen-specific antibody was made locally by cells in the lung.

Albumins↗
PubMed1982

The evaluation of lung immunity in chimpanzees.

The development of immunity in the chimpanzee was evaluated at 5 through 14 days after the deposition of a particulate antigen into a single lung lobe. An increased number of IgA, IgM, and IgG antibody-forming cells were found in the immunized lung lobes and in the blood. Few antibody-forming cells were found in the control lung lobes. The results from the chimpanzees were qualitatively the same as those from previous studies in which single lung lobes of dogs were immunized. However, a higher number of IgA antibody-forming cells was observed in the lavage fluid from chimpanzees than in that from dogs.

Animals↗
PubMed1982

Recruitment of antibody-forming cells in the lung after local immunization is nonspecific.

The deposition of particulate antigen into the dog lung induces a large accumulation of antigen-specific-forming cells in immunized lung lobes. The results of our previous studies with dogs indicate that these cells are recruited to the immunized lung lobes from the blood. The present study was designed to determine if the recruitment of immune cells to the lung is antigen-specific, or if changes occur in the lung after immunization that allow immune cells to enter the lung nonspecifically. Dogs were immunized in the left and right cardiac lung lobes with antigenically different particulate antigens. The number of lymphoid cells producing antibody to each antigen and the concentrations of antigen-specific antibody were measured in the immunized lung lobes and in a control lung lobe at 5 through 14 days after immunization. Similar numbers of antibody-forming cells and concentrations of antibody to both antigens were found in each immunized lung lobe, regardless of which antigen was used for immunization. These results indicate that antigen exposure alters the lung to allow a nonspecific recruitment of immune cells from the blood into the immunized lung lobes, regardless of antigen specificity. These data also provide further evidence that the antibody-forming cells found in the lung lavage fluid after localized immunization are produced in the thoracic lymph nodes or other systemic lymphoid tissues, rather than locally in lymphoid tissues in the deep lung.

Animals↗
PubMed1982

Flexible fiberoptic bronchoscopy of chimpanzees.

Five 10- to 12-year-old, male chimpanzees were used in a study that required repeated flexible fiberoptic bronchoscopic procedures. The combination of ketamine and inhalation anesthesia was satisfactory for these procedures. The gross anatomy of the airways of the chimpanzee resembled those of man more than those of the dog or rhesus monkey. The bronchoscope could be easily maneuvered into the main bronchi, lobar bronchi, and at least two branches of the lobar airways. Sublobar lavages were performed to obtain cells from the deep lung. Histologic examination of a lung showed that generous numbers of bronchial glands extended down to the tertiary bronchi in chimpanzees explaining the copius amounts of mucous observed during bronchoscopy.

Anesthesia, Endotracheal↗
PubMed1980

Cellular immunity induced by lung immunization of Fischer 344 rats.

This study describes immunologic response in lung-associated lymph nodes, spleen, cervical lymph nodes and lung lavage cells of rats immunized by intratracheal instillation of BCG-sheep red blood cell (SRBC) suspensions. At 4 through 17 days after immunization, the number of anti-SRBC IfM and IgG antibody-forming cells was significantly increased only in the lung-associated lymph nodes, indicating that these tissues retain the particulate antigen that was deposited in the lung. In contrast, cellular immunity was found initially in the spleen, with significant responses in the lungs and in the lung-associated lymph nodes on 13--19 days after immunization. Our data indicated that the lung-associated lymph nodes are probably the initial site for the production of antigen-sensitive lymphocytes for both antibody and cellular immunity after lung immunization. Cells responsible for cellular immunity appear to migrate to the spleen, where further cell division take place.

Animals↗
PubMed1980

Immune responses after localized lung immunization in the dog.

The immune response in immunized and unimmunized bronchoalveolar spaces, as well as in the blood, was measured after localized deposition of antigen in the lung. Using a fiberoptic bronchoscope, groups of dogs were immunized with sheep red blood cells (SRBC) deposited into a single airway of the left apical or right apical lung lobes. Bronchoalveolar cells were obtained by lung lavage through the fiberoptic bronchoscope from the immunized lung lobe, as well as from lung lobes that did not receive antigen. Lavage cells and blood samples were collected at 3 to 21 days after immunization. The total number of lymphocytes, macrophages, and polymorphonuclear leukocytes, and the number of lymphoid cells producing anti-SRBC IgM and IgG antibodies were determined. Our results indicated that the highest number of antibody-forming cells (AFC) were found in the immunized lung lobes. An elevated, but significantly lower number of AFC were observed in the unimmunized lung lobes. The number of IgM and IgG AFC in the blood reached peak concentrations 3 to 7 days earlier than the AFC in the lung. We concluded from our data that the blood is an important source of the AFC found in the lung.

Animals↗