Conglomerates of tubular structures in BCG-induced alveolar macrophages revealed by negative staining.
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Biomedical subjects
Publications and source records attributed to Q N Myrvik.
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Compared to cells from normal rabbit lungs, BCG-induced alveolar macrophages have a marked increase in hydrolase levels and the number of large electron-dense subcellular structures. This study was performed to investigate the possibility that these electron-dense structures were responsible for the increased hydrolase levels of these cells. Using sucrose gradient centrifugation, nuclei-free homogenates of normal and BCG-induced macrophages were analyzed with respect to the subcellular particles they contain. Gradient fractions were assayed for enzymes commonly associated with lysosomes as well as the mitochondrial cytochrome oxidase. Fractions of peak hydrolase activity from the BCG-induced preparations were consistently more dense than those from the normal cell preparations. Ultrastructural studies of the particulate material found in fractions of peak hydrolase activity from BCG-induced preparations revealed the presence of electron-dense, often dumbbell-shaped, granules. The data suggest that these peculiar granules are responsible for the elevated hydrolase levels of BCG-induced alveolar macrophages.
The specificity of Bacillus Calmette Guérin (BCG)-induced accelerated pulmonary granuloma formation has been evaluated in rabbits by cross sensitization-challenge experiments by using another granulomagenic organism, Corynebacterium granulosum. BCG-sensitized rabbits responded to challenge with homologous but not heterologous antigen, indicating that BCG-induced accelerated granuloma formation displays specificity characteristic of immunological reactions. These differences were also observed in local pulmonary delayed hypersensitivity, as determined by the migration inhibition test. The relationship between local pulmonary delayed hypersensitivity and the accelerated granulomatous response is discussed.
The role of local pulmonary delayed hypersensitivity in accelerated pulmonary granuloma formation was investigated using cortisone acetate, an immunosuppressive drug that appears to preferentially eliminate committed lymphocytes at appropriate doses. Data are presented showing that cortisone acetate suppressed local pulmonary delayed hypersensitivity at the time of and subsequent to challenge with BCG. Furthermore, cortisone damage appeared to involve primarily committed lymphocyte populations since the defect was repairable with sensitized spleen cells, an unlikely source of macrophage precursors.
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The role of cord factor in BCG-induced pulmonary granulomas and local pulmonary delayed hypersensitivity (DH) was evaluated. Cord factor did not induce pulmonary granulomas comparable to those induced by killed BCG. The compound did not induce pulmonary DH that could be elicited by itself, purified protein derivative, or BCG. Cord factor-injected animals did not develop an accelerated pulmonary granulomatous response after challenge with killed BCG. Finally, cord factor did not elicit local pulmonary DH in BCG-sensitized animals. These results are discussed in relation to cord factor's role in antimicrobial immunity, granuloma formation, and antitumor immunity.
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Anti-rabbit alveolar macrophage goat serum (AMS), adsorbed of hemolysins and hemagglutinins, exhibited complement-dependent cytotoxicity for the following rabbit target cells: alveolar macrophages, thymocytes, and kidney (RK-13) cells. The intravenous injection of AMS, sufficient to reduce markedly the dermal tuberculin reaction in BCG-sensitized rabbits, did not suppress the development of BCG-induced chronic and accelerated pulmonary granulomas. These observations are discussed in relation to delayed sensitivity, allergic granuloma formation, and cell-associated immunity.
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