Bronchopulmonary humoral and cellular enhancement in experimental silicosis.
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Biomedical subjects
Publications and source records attributed to R P Stankus.
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The bronchopulmonary cellular immunological response to repeated intratracheal inoculation of aluminum chlorhydrate, sodium zirconium lactate, and zirconium aluminum glycine was examined in rabbits. Results of a dose-response experiment using 0.1, 1.0, and 10.0-mg intratracheal inoculations of each metallic salt demonstrated significant bronchopulmonary histopathology in the 10.0-mg dose-response groups only. Acute lesions were histologically characterized by an inflammatory response centered around respiratory bronchioles. Although epithelioid cell formation was evident in 10.0 mg of aluminum salt (aluminum chlorhydrate and zirconium aluminum glycine) -injected animals, no well-defined granulomas characterized by an orderly arrangement of epithelioid cells, lymphocytes, and giant cells were evident in any of the experimental groups employed. All three metallic salts induced "activated" bronchopulmonary macrophages as determined by an in vitro phagocytic assay. This activation was likely nonimmunological since no measurable differences were observed in metallic salt-induced delayed skin reactivity or migration inhibition factor production between inoculated and uninoculated rabbits. The above observations suggest that aluminum and zirconium salts administered in comparatively high dosage via the respiratory tract route can induce respiratory bronchiolitis and activation of alveolar macrophages in the absence of demonstrable delayed hypersensitivity.
Repeated intratracheal (IT) inoculation of rabbits with a homogenized, saline suspension of Micropolspora faeni produced bronchopulmonary (BP) histologic lesions resembling those of human hypersensitivity pneumonitis. With an in vitro phagocytic and bactericidal assay, an analysis of BP macrophages from M. faeni-injected rabbits demonstrated activation at both 2 and 4 weeks after the initiation of immunization. No BP macrophage activation was observed in immunized rabbits 6 weeks post-inoculation. BP macrophage activation was capable of recall after 6 weeks in M. faeni-sensitized animals that received a booster IT injection (2 mg) that did not activate "normal" alveolar wash cells. This recall of BP macrophage activation was accompanied by both a marked migration of mononuclear cells into the lung and positive delayed hypersensitivity skin reactions after intradermal injection of M. faeni antigen. Pulmonary histologic examination of sensitized, boosted rabbits suggested an enhanced cellular parenchymal infiltrate when compared with appropriate controls. The above observations confirm the occurrence of immunologically activated BP macrophages in rabbits inoculated witn M. faeni via the respiratory tract route and suggest a correlation between macrophage activation and histopathology.
Antisera obtained from selectively bred Sprague-Dawley rats after a primary series of immunization with group A streptococcal vaccine exhibit specific anti-carbohydrate antibodies of restricted heterogeneity. Separation of anti-carbohydrate antibodies was achieved on the basis of differences in the relative binding affinities of the antibodies for an insoluble, hapten (N-acetyl-D-glucosamine) immunoadsorbent. Evaluation of several eluting reagents including hapten, thiocyanate, urea and acid-salt demonstrated the chaotropic ion thiocyanate to be most effective in separating anti-hapten populations of individual affinity characteristics. In general, there was no consistent relationship between the net electrical charge of an antibody and its relative binding affinity for the immunoadsorbent. Furthermore, non-precipitating rat anti-streptococcal A carbohydrate antibodies were characterized as antibodies of relatively low binding affinity for the hapten immunoadsorbent. From a practical point of view, thiocyanate is recommended for the routine elution of anti-carbohydrate antibodies from innumoadsorbents.
The heavy (H) chains of three anti-streptococcal group A carbohydrate antibodies (anti-SACHO) of restricted heterogeneity, elicited in inbred Sprague-Dawley rats, were subjected to 40 cycles of automated Edman degradation. All three antibody H-chain preparations had an identical amino acid sequence and were classified as a variant of the VHIII subgroup of immunoglobulin H chains. A comparison of the H-chain sequence of these antibodies with that of pooled rat gamma chains suggests that a very minor population of H chains (closely related to the VHIII subgroup) has been 'recruited' as a consequence of this immunization. This observation further supports the notion that 'framework' and 'specificity' or 'hypervariable regions' are closely linked.
The concentrations of IgA, IgM and IgY were measured in gallbladder (GB) bile and serum from chickens of various ages. The ontogeny data suggested that IgA and IgY were synthesized by the GB. Furthermore, the chicken GB becomes lymphoid 3-8 days post-hatch and contains distinct foci of lymphocytes by 7 weeks of age. That the GB can synthesize and secrete IgA was shown in two ways. IgA-containing cells were demonstrated by immunofluorescence and in vitro studies with adult GB explants showed the synthesis and secretion of IgA and also IgY and IgM. Immunoglobulin class suppression experiments and quantitation of IgA in sera from selected sites supported the concept of synthesis and secretion of IgA by the GB. Several lines of evidence also support the concept of some bile IgA being derived from serum. Introduction of antigen directly into the GB was shown to stimulate antibody formation, and this antibody was detectable in bile and serum. A very unusual finding, in one animal, was the presence of a normal secretory IgA concentration in the presence of undetectable serum IgA. These data indicate that the GB is an integral part of the secretory immunological system and suggest that aberrations in GB-immune function may result in pathological clinical manifestations.
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