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Chapter 4 : Liquefaction of Caseous Foci and Cavity Formation

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Liquefaction of Caseous Foci and Cavity Formation, Page 1 of 2

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Abstract:

The chronic human-type tuberculosis with liquefaction and cavity formation is easily produced in rabbits, but it is not as easily produced in guinea pigs and cannot be produced in mice. Liquefaction of solid caseous foci in the lung perpetuates tuberculosis in humans because such liquefaction enables the extracellular growth of tubercle bacilli and the formation of cavities that discharge such bacilli into the airways and into the environment. Pulmonary cavities were produced in 2 to 4 weeks by the injection of various materials (emulsified in paraffin oil and lanolin) through the chest wall directly into the lungs of rabbits. Azathioprine, an immunosuppressive drug, also prevented cavities, probably by reducing the amount of delayed-type hypersensitivity (DTH). Hydrolytic enzymes play a major role in liquefaction and cavity formation. Products resulting from the hydrolysis of proteins and other macromolecules increase the osmolarity of the caseum. The tracheobronchial lymph nodes were slightly enlarged and occasionally contained tuberculous granulomas. Humans with well-controlled clinical tuberculosis may not show as great a reduction in tuberculin sensitivity. In clinical tuberculosis, a frequent occurrence is blood-tinged sputum and occasionally frank hemoptysis. The alveolar macrophages frequently had a vacuolated appearance, probably from the ingestion of surfactant. Mycobacterium vaccae is a rapidly growing avirulent acid-fast bacillus that was originally found free in the pastures of cattle and in their milk. Drugs that prevent a composition favorable to extracellular bacillary growth would be a welcome addition to our control of this disease.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Figures

Image of FIGURE 1
FIGURE 1

A multiloculated cavity in the lung of a rabbit (#8, Experiment I) that had inhaled 620 virulent bovine-type tubercle bacilli (Ravenel S) 19 weeks previously. The hole at the upper right side of the photograph is an intact bronchus. The hole at the lower left is part of the loculated cavity. The center of each is black because the back was sliced from the specimen to stabilize it for photography. Note the fibrosis around the large cavity in the center of the photograph. Magnification, ×3. Reprinted with permission from reference 20.

This is an example of the slowly progressive cavitary disease frequently found in humans (see chapter 3).

Note:Table 2 of reference 20 lists the necropsy findings on each rabbit that lived 18 or more weeks in the three experiments that we performed. I did not reproduce the entire table in this chapter but have listed the rabbit and experiment numbers in many of the figures, so that interested readers can easily obtain (from reference 20) more details on the characteristics of disease in the rabbits providing the specimens for these photographs.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 2
FIGURE 2

Multiple cavities in the upper part of the right lower lobe of the lung of a rabbit (#5, Experiment III) euthanized 33 weeks after the inhalation of 340 virulent bovine-type tubercle bacilli. These are mostly secondary and tertiary cavities that developed locally from the bronchogenic spread of large numbers of bacilli from one or two primary lesions. Despite the extensive tuberculosis in the upper part of this lobe, no secondary lesions were grossly visible in the lower part. In addition, the whole left lung of this rabbit was free of grossly visible tuberculous lesions. Magnification, ×1. Reprinted with permission from reference 20.

This is an example of the local nature of tuberculosis and the efficacy of acquired (adaptive) immunity that prevents the progress of tuberculous lesions arising elsewhere from relatively low numbers of inhaled bacilli.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 3
FIGURE 3

Specimen sliced from the right side of the right lower lobe of rabbit #5, Experiment III (Fig.2). Note the absence of functional lung tissue, the large size of the cavities, the residual semisolid caseous tissue (center), and the extensive fibrosis. Magnification, ×4.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 4
FIGURE 4

Tuberculous lesions in the right upper lobe of rabbit #5 (Experiment III). (The right lower lobe of this rabbit is depicted in Fig. 2.) Two large cavities have been sliced open. Note that most of the lesions are well encapsulated with fibrous tissue. Fibrous encapsulation of tuberculous lesions is common in chronic human cavitary disease. Magnification, ×2.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 5
FIGURE 5

Tuberculous laryngitis in a rabbit (#4, Experiment III) that had inhaled 300 virulent bovine-type tubercle bacilli 33 weeks previously. The lung of this rabbit had 14 lesions, 4 of which had formed cavities. A cavity in the right lower lung apparently discharged so many bacilli into the bronchial tree that the larynx became infected. Eventually, the airway became partly obstructed, so the animal was breathing with difficulty at the time it was euthanized. Magnification, ×5.4. Reprinted with permission from reference 20.

Before antimicrobials were available to treat tuberculosis, a similar tuberculous laryngitis occasionally occurred in humans. Such patients required a tracheotomy to stop the labored breathing.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 6
FIGURE 6

A caseous tubercle at the bifurcation of a bronchus near the hilus in a rabbit (#12, Experiment III) that had inhaled 420 virulent bovine-type tubercle bacilli (Ravenel S). We euthanized this rabbit at 30 weeks, because it had labored breathing. Magnification, ×4.9. Reprinted with permission from reference 20.

Before antimicrobials were available to treat tuberculosis, similar lesions occasionally occurred in the bronchial tree in human beings.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 7
FIGURE 7

A caseous tubercle partly obstructing the lumen of the trachea (above) and constricting the esophagus (bisected below) (rabbit #12, Experiment III). Magnification, ×4.9.

The esophageal constriction apparently caused such malnutrition that the resistance of the rabbit was decreased and many small metastatic pulmonary lesions developed.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 8
FIGURE 8

Pulmonary tuberculosis in the left lung of a rabbit (#8, Experiment II) that had inhaled 5,500 virulent bovine-type tubercle bacilli 18 weeks previously. The pleural surface of the lung is roughened by numerous coalescing tubercles. Magnification, ×1.2.

Tuberculous pleurisy frequently occurs in humans due to similar lesions just below the pleural surface (see chapter 3).

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 9
FIGURE 9

The same lung shown in Fig. 8, bisected horizontally. The lung contains numerous primary and secondary lesions and many minute cavities. Note how little functional pulmonary tissue remains in the upper lobe. Magnification, ×1.2.

Similar local consolidation occurs in humans (see chapter 3).

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 10
FIGURE 10

Pulmonary cavities from two rabbits (in high-dose Experiment II) that had inhaled about 5,000 virulent bovine-type tubercle bacilli 18 weeks previously. Below each cavity are encapsulated fibrotic lesions with large semisolid caseous centers that had not discharged into bronchi. The amount of softening of the caseous material cannot be accurately assessed in formalin-fixed tissues, because it is hardened by the fixation process. At necropsy, the consistency of the caseum varied from that of a “hard” cheese to that of a rather “soft” cheese. Magnification, ×2.7. Reprinted with permission from reference 20.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 11
FIGURE 11

Walled-off tuberculous lesions from the lungs of rabbits (in high-dose Experiment II) 18 weeks after the inhalation of about 5,000 virulent bovine-type tubercle bacilli. In the specimen on the right, there are several semisolid caseous lesions with thick fibrous capsules and one cavity. In the specimen on the left, the amount of fibrosis is so extensive that little functional lung tissue remains. Magnification, ×3.1. Fibrocaseous tuberculosis is a frequent occurrence in humans.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 12
FIGURE 12

A glycol methacrylate-embedded tissue section of a tuberculous lesion, from a rabbit (#8, Experiment I) that had inhaled 620 virulent bovine-type tubercle bacilli 19 weeks previously. The section was stained histochemically for β-galactosidase, which is our marker for activated macrophages: the darker the blue color produced, the more activated the macrophage (see chapter 6). This photograph shows portions of three caseous centers, surrounded by tuberculous granulation tissue containing numerous β-galactosidase-positive macrophages (epithelioid cells). Peripheral to these macrophages are lymphocytes, plasma cells, fibroblasts, and unactivated (β-galactosidase-negative) macrophages. At the lower left are a few alveoli (with thickened walls) containing accumulations of highly activated alveolar macrophages, which are easily recognized by their dark β-galactosidase-staining cytoplasm. Counterstained with Giemsa. Magnification, ×100. Reprinted with permission from reference 20.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 13
FIGURE 13

A glycol methacrylate-embedded tissue section of a tuberculous lesion from a rabbit (#8, Experiment I) that had inhaled 620 virulent bovine-type tubercle bacilli 19 weeks previously. This section was stained for acid phosphatase, a bright-red color (black in this photograph). Acid phosphatase is another marker for macrophage activation (see chapter 6).

The edge of a cavity is at the lower right. Next (proceeding to the upper left) are unstained macrophages (epithelioid cells), some of which are disintegrating, and then an area containing many acid phosphatase-positive macrophages. The outer layer (upper left) is the surrounding capsule containing many fibroblasts, a few of which also stain positive for acid phosphatase. The dark circle in the capsule is a metaplastic alveolus (see Fig. 21–24). Not all of the mature epithelioid cells (large cells with a rounded outline) stain positive for acid phosphatase, indicating heterogeneity in this cell population (see reference 40). Counterstained with Giemsa. Magnification, ×330. Reprinted with permission from reference 20.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 14
FIGURE 14

A tissue section of the wall of a tuberculous cavity produced in a rabbit (#4, Experiment I) that had inhaled 880 virulent bovine-type tubercle bacilli 22 weeks previously. Immunostained for cathepsin D, a major proteinase of macrophages.

Intact bronchial epithelium is shown at the upper right. At the lower left, this epithelium is ruptured, allowing the liquefied caseum in the cavity (below) to be discharged into the bronchus. Cathepsin D (a brown color not easily identified in this black and white photograph) is present in both live and dead macrophages (epithelioid cells) adjacent to the liquefied caseum. This finding suggests that cathepsin D plays an important role in the liquefaction process. Immunostained with polyclonal goat antibody to rabbit cathepsin D and the avidin-biotin peroxidase technique. Magnification, ×420. Reprinted with permission from reference 20.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 15
FIGURE 15

A tissue section of a rabbit pulmonary cavity wall. A small blood vessel extends into the cavity’s lumen at the right of the photograph. Such exposed vessels are the source of blood in the sputum. In humans, when a larger blood vessel is similarly exposed in a cavity and ruptures, massive hemoptysis and sometimes fatal hemorrhage may occur.

Adjacent to the small blood vessel in this photograph are disintegrating mature epithelioid cells. Lurie (4, 48) showed that such large ovoid cells have destroyed many of the bacilli that they once contained. However, adjacent to the liquefied caseum in the wall of the cavity, the concentration of bacillary tuberculin-like products is often too high for such epithelioid cells to survive very long. The glycol methacrylate-embedded tissue section was stained with Giemsa. Magnification, ×400. Reprinted with permission from reference 20.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 16
FIGURE 16

An area slightly deeper into the cavity wall than that depicted in Fig. 15. In the center are macrophages containing dark-staining granules. These macrophages occur in some places within the cavity wall, but, in most places, nongranulated macrophages predominate. The nature of these granules is unknown (see text).

Part of the capsule (which surrounds this cavitary lesion) is shown at the left of the photograph. It contains fibroblasts and some lymphocytes and plasma cells. Many of the fibroblasts contain translucent (probably secretory) granules. The glycol methacrylate-embedded tissue section was stained with Giemsa. Magnification, ×600. Reprinted with permission from reference 20.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 17
FIGURE 17

A tissue section of the liquefied caseum in a pulmonary lesion of a rabbit (Experiment II) that had inhaled about 5,000 virulent bovine-type tubercle bacilli 7 weeks previously. The bacilli were stained with TB Fluorostain (rhodamine B/auramine 0) (Polysciences, Inc., Warrington, Pa.) and visualized with an epifluorescent microscope at wavelengths 495 nm (excitation) and 535 nm (emission). Liquefied caseum contains variable numbers of tubercle bacilli, both microscopically in tissue sections and by culture (see Table 5). Magnification, ×400.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 18
FIGURE 18

A tissue section of a portion of the cavity wall. Bacilli can be seen in the clear spaces (possibly lymphatics) found among the intact and disintegrating mature epithelioid cells. Liquefied caseum is shown in the lower left corner of the photograph. The glycol methacrylate-embedded tissue section (1 to 2 μm thick) was stained with carbol-fuchsin and Giemsa. Magnification, ×1,200.

In rabbits (and humans) with cavitary tuberculosis, tubercle bacilli enter the lymphatics and the microvasculature. However, the native and acquired resistance of such hosts is usually so high that metastatic lesions arising by the lymphogenous and hematogenous routes usually fail to progress. Progressive metastatic pulmonary lesions arise in such resistant hosts when large numbers of tubercle bacilli enter the airways from the cavity. In this case, many bacilli may land in one site and may be difficult for the host to control.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 19
FIGURE 19

A tissue section of a rabbit pulmonary tuberculous lesion (rabbit #4, Experiment III) showing virulent bovine-type tubercle bacilli that had grown profusely in liquefied caseum. On the left, the lesion was probably beginning to cavitate, because some of the spaces in the liquefied caseum seem larger than usual. Such profuse growth occurs only in some lesions with liquefied centers (see Table 5), presumably where the composition of the liquefied caseum is most favorable and/or the adaptation of the bacillus to extracellular growth is most complete. Stained with carbol-fuchsin, counterstained with methylene blue. Magnification, ×600. Reprinted with permission from reference 37.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 20
FIGURE 20

A tissue section of the wall of a rabbit pulmonary cavity (rabbit #5, Experiment III) showing virulent bovine-type tubercle bacilli growing in the liquefied caseum. The bacilli are growing more profusely near the lumen of the cavity (on the left) where the oxygen tension is highest. Stained with carbol-fuchsin, counterstained with methylene blue. Magnification, ×250. Reprinted with permission from reference 37.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 21
FIGURE 21

A tissue section of the wall of a rabbit pulmonary cavity (Experiment II) 18 weeks after the inhalation of about 5,000 virulent bovine-type tubercle bacilli. To the right is the cavity’s air space. Next to it is the adjacent liquefied caseum. In the middle of the photograph is the fibrous capsule. The area at the left contains alveoli (saccules) with metaplastic epithelium and a few large macrophages in the air space. Between these metaplastic alveoli are macrophages, plasma cells, lymphocytes, fibroblasts, and dilated microvessels (probably venules). The glycol methacrylate-embedded tissue section was stained with Giemsa. Magnification, ×125. Reprinted with permission from reference 20.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 22
FIGURE 22

Another portion of the same cavity as in Fig. 21, shown at higher magnification to identify the types of cells present. A thick fibrous capsule (upper half) surrounds the liquefied caseum (below). The capsule contains many fibroblasts, as well as some macrophages, lymphocytes, and plasma cells. An oval metaplastic alveolus and a small dilated blood vessel are present on the right. Upon fixation, liquefied caseum often contains spaces between the coagulated proteins, whereas solid caseum usually does not.

On gross examination, all gradations of caseum fluidity were found among the various lesions. The gross examination is a more accurate test of fluidity, because fixation solidifies the proteinrich material. The glycol methacrylate-embedded tissue section was stained with Giemsa. Magnification, ×250.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 23
FIGURE 23

An alveolus (saccule) with metaplastic epithelium containing alveolar macrophages in the wall of the same cavity shown in Fig. 21 and 22. Many of the alveolar epithelial cells are vacuolated, and the macrophages within this alveolus are also vacuolated (see text). Nearby are areas rich in lymphocytes and plasma cells, containing dilated capillaries or venules. Accumulations of plasma cells and dilated microvessels are frequent components of tuberculous granulation tissue. The glycol methacrylate-embedded tissue section (cut 1 to 2 μm) was stained with Giemsa. Magnification, ×350.

Metaplastic alveoli probably arise from partial obstruction of the connecting bronchus. They no longer function in the oxygenation of blood.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 24
FIGURE 24

A tissue section of a rabbit pulmonary cavity wall (Experiment II) 18 weeks after the inhalation of about 5,000 virulent bovine-type tubercle bacilli. The lumen of the cavity is at the right. Less fibrosis is present than that in Fig. 21 and 22, and the metaplastic alveoli are closer to the cavity lumen. Several dark acid-phosphatase-positive macrophages are present in the cavity wall, as well as in the lumen of the metaplastic alveoli. The glycol methacrylate-embedded tissue section (cut 1 to 2 μm) was stained for acid phosphatase and counterstained with Giemsa. Magnification, ×210.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 25
FIGURE 25

A tissue section of a rabbit dermal BCG lesion, 28 days of age, immunostained for cathepsin D, a major macrophage proteinase. The caseous center has liquefied and ulcerated. The viable and dead macrophages surrounding the liquefied caseum contain high levels of cathepsin D. The dead macrophages within the liquefied caseum and the viable macrophages in the more peripheral tuberculous granulation tissue contain much-reduced levels of this proteinase. Stained with goat antiserum to cathepsin D, rabbit anti-goat immunoglobulin (in excess), horseradish peroxidase–goat antiperoxidase complex, hydrogen peroxide, and 3-amino-9-ethylcarbazole. No counterstain. Magnification, ×100. Reprinted with permission from reference 21.

Note how closely this ulcerating dermal BCG lesion resembles the pulmonary cavitary lesion that was produced by an aerosol of virulent bovine-type tubercle bacilli and shown in Fig. 14. Cathepsin D has a similar distribution in both lesions. Experiments to study factors involved in liquefaction and cavity formation, as well as drugs to inhibit such factors, could be performed with dermal BCG lesions and then confirmed with virulent tubercle bacilli in the lungs.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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Image of FIGURE 26
FIGURE 26

A tissue section of a rabbit dermal BCG lesion, 28 days of age, stained for the lysosomal enzyme β-galactosidase, our marker for activated macrophages. As in Fig. 25, the caseous center has liquefied and ulcerated. The viable and dead macrophages surrounding the liquefied caseum (in the top third of the photograph) contain the highest levels of β-galactosidase. The dead macrophages within the liquefied caseum contain little β-galactosidase, and the viable macrophages in the peripheral tuberculous granulation tissue (in the lower half of the photograph) show reduced levels of this hydrolytic enzyme. Stained with 5-bromo-4-chloro-3-indolyl-β--galactoside, lightly counterstained with hematoxylin. Magnification, ×100. Reprinted with permission from reference 21.

This figure demonstrates that macrophages at the edge of liquefying caseum become highly activated for lysosomal enzymes. Lysosomal proteinases, nucleases, and lipases seem to be major causes of liquefaction.

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
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References

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1. Rich, A. R. 1951. The Pathogenesis of Tuberculosis, 2nd ed. Charles C Thomas Publisher, Springfield, Ill.
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Tables

Generic image for table
TABLE 1

Causes and results of liquefaction a

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
Generic image for table
TABLE 2

Data on rabbits dying of pulmonary tuberculosis in the high-dose Experiment II

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
Generic image for table
TABLE 3

Ratios: number of inhaled bovine-type tubercle bacilli that produced one grossly visible primary pulmonary lesion in commercial rabbits a

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
Generic image for table
TABLE 4

M. vaccae immunotherapy of rabbits with active tuberculosis produced by the inhalation of virulent bovine-type tubercle bacilli (Ravenel S) a

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4
Generic image for table
TABLE 5

Number of tubercle bacilli cultured from the liquefied caseum in selected lesions from rabbits in low-dose Experiment III at 33 weeks a

Citation: Dannenberg, Jr. A. 2006. Liquefaction of Caseous Foci and Cavity Formation, p 65-94. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch4

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