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Biomedical subjects

V L Moore

Publications and source records attributed to V L Moore.

At least 55 records · Page 3Linked to original sources
PubMed1982

Experimental murine hypersensitivity pneumonitis: multigenic control and influence by genes within the I-B subregion of the H-2 complex.

An animal model of hypersensitivity pneumonitis was developed in the mouse by immunization with pigeon dropping extract (PDE) in complete Freund's adjuvant, followed by daily aerosol challenge with soluble specific antigen. C3H/He (H-2k) mice developed intense diffuse interstitial lung disease and were classified as high responders. On the other hand C57BL/10 (H-2b) mice developed only mild perivascular infiltration. Moreover, although high-responder C3H/He mice developed delayed hypersensitivity to PDE, low-responder C57BL/10 mice failed to develop this reactivity. Breeding studies in F1 and F2 progeny of C3H/He high responders and C57BL/10 low responders showed that responsiveness was multigenic. B10.BR (H-2k) mice also developed intense PDE-induced diffuse interstitial lung disease, suggesting that genes within the H-2 complex influence the development of pulmonary inflammation. On the other hand, C3H.SW (H-2b) mice were also high responders, possibly because of non-H-2 genes in the C3H/He background that influenced responsiveness. Studies in H-2 recombinant strains with C57BL/10 backgrounds mapped the H-2-linked genes that influence responsiveness within the I-B subregion.

Alveolitis, Extrinsic Allergic↗
PubMed1982

Enhancement of systemic immune response by immunization into chronically inflamed lungs.

Intrapulmonary instillation of proteins into rabbit lungs with BCG-induced granulomatous inflammation results in greater transport of these molecules into the blood, and the primary route is probably the pulmonary lymphatics. In addition, rabbits with inflamed lungs develop a more potent systemic immune response when exposed to soluble antigens as an aerosol. The current study was done to further study the mechanisms of this phenomenon using the Jerne plaque technique. Intrapulmonary immunization with soluble antigens (solubilized SRBCs and HSA) resulted in a greater PFC response to both antigens when the lungs exhibited BCG-induced granulomatous inflammation. A previous study demonstrated that more antigen administered intratracheally was found in the HLNs when the lungs displayed granulomatous inflammation. However, in the present study, we did not observe an enhanced PFC response in HLN cells when antigens were introduced into inflamed lungs. When rabbits with BCG-inflamed lungs were immunized i.v., they did not develop an enhanced PFC response in the spleen. Immunization into the respiratory tract of normal rabbits with large doses (300 micrograms) of soluble antigens also resulted in a substantial PFC response in the spleen that was quantitatively greater than that induced by the same i.v. dose. These data indicate that (1) administration of antigens into inflamed lung results in an enhanced systemic immune response, (2) although larger quantities of soluble antigens administered by the pulmonary route accumulate in the HLN when lungs are inflamed, cells from this tissue do not exhibit an enhanced PFC response, and (3) large doses of soluble antigens instilled into normal lungs induce a greater systemic immune response that the same doses administered i.v. This study further demonstrates the importance of pulmonary inflammation and the immune response to inhaled antigens and provides insight as to how individuals with chronic inflammatory lung disease can react in an augmented fashion to environmental antigens.

Alveolitis, Extrinsic Allergic↗
PubMed1981

Genetic basis of BCG-induced suppression of delayed hypersensitivity.

BCG can either act as an adjuvant to potentiate immunological responses or, in some cases, can induce suppression. The reasons for these differential activities are not clear but may include routes and doses of administration, as well as variable host reactivity to the agent. In this study, we have used killed BCG administered intravenously to produce chronic granulomatous inflammation (CGI) in the lungs and spleen of inbred mice. We report that strains which develop CGI were usually anergic, as evaluated by the development of delayed hypersensitivity (DH) to sheep erythrocytes (SRBC). Studies on the genetics of BCG-induced anergy indicated that it was unigenic, recessive and linked (approximately 28 recombination units) to the immunoglobulin heavy-chain allotype (Igh). There was no influence by genes linked to the major histocompatibility complex. The study indicates that anergy associated with CGI is under genetic control, which may explain the variability of anergy in patients with granulomatous diseases. The implication of linkage to the Igh complex is not clear, but it may be associated with VH receptors on T lymphocytes, which in turn act on macrophages to mediate suppression.

Animals↗
PubMed1981

Serum angiotensin-converting enzyme levels in patients with pigeon-breeder's disease.

The serum concentration of angiotensin-converting enzyme is frequently elevated in individuals with active sarcoidosis. The enzyme is presumably actively synthesized by the epithelioid and giant cells of the granuloma. Hypersensitivity pneumonitis, resulting from the inhalation of antigens from pigeons by susceptible individuals, is associated with the development of a granulomatous interstitial and alveolar infiltrate in the pulmonary parenchyma. Because the clinical and pathologic presentation may mimic that of sarcoidosis, we compared the serum levels of angiotensin-converting enzyme in these two diseases. The concentration of angiotensin-converting enzyme is not elevated in individuals with active hypersensitivity pneumonitis, in contrast to its frequent elevation in sarcoidosis. We suggest that the granulomatous response in hypersensitivity pneumonitis may differ at a biochemical level from that of sarcoidosis, since the synthesis of angiotensin-converting enzyme does not appear to be increased.

Allergens↗
PubMed1981

Strain variation in BCG-induced chronic pulmonary inflammation in mice: control by a cyclophosphamide-sensitive thymus-derived suppressor cell.

We previously reported that only certain strains of inbred mice develop intense chronic granulomatous inflammation (CGI) in the lungs and spleen in response to an i.v. injection of killed BCG in an oil-in-saline emulsion (BCG-E). The capacity to respond did not appear to be controlled by genes within the H-2 complex; subsequent studies have shown that genes linked to the Igh allotype complex influence the development of CGI. In other systems, unresponsiveness to certain antigens has been shown to be because of cyclophosphamide- (Cy) sensitive suppressor cells. We therefore used Cy as a probe to study mechanisms of unresponsiveness in low-responder (LR) CBA mice. The results indicate that LR mice could be converted into high responders (HR) by treatment with 100 mg of Cy per kilogram of body weight 2 days before injection with BCG-E. In addition, the effects of Cy were inhibited by the provision of syngeneic whole or purified spleen T cells from mice injected 7 days previously with BCG-E. Cells responsible for abolition of the Cy effect were sensitive to anti-Thy-1 serum + C. Thus, the intensity of BCG-E-induced CGI in mouse lungs is controlled by a population of Cy-sensitive T lymphocytes.

Animals↗
PubMed1980

Chronic pulmonary inflammation modulates the fate of proteins administered by the respiratory tract.

The systemic appearance of radioiodinated proteins (125I-OA and 131I-HSA) administered via the respiratory route was studied in normal rabbits and in rabbits with BCG-induced chronic granulomatous pulmonary inflammation. The proteins were administered by i.t. injection into intact rabbits and into rabbits with tracheal cannulas or as an aerosol into isolated perfused lungs. The results showed that radioactivity appeared in the circulation as two fractions, one that was precipitables with 5% TCA and therefore protein-bound and one that was soluble in TCA. In both intact and tracheostomized animals, significantly more protein-;ound radioactive iodine was detected in the circulation of BCG-treated animals than in normal animals as early as 15 min after i.t. injection, and the differences persisted from 2 to 4 hr. However, in the isolated perfused lung, in which the only route for protein uptake into the circulation was the alveolocapillary barrier, only minimal differences in blood protein levels were observed as compared to normal BCG-inflamed lungs. This study suggests that chronic pulmonary inflammation promotes the absorption of i.t.-injected protein into the circulation, and that the route of enhanced uptake into blood is not the alveolocapillary membrane.

Animals↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗