The Role of Macrophages in Particle Translocation from Lungs to Lymph Nodes

Harmsen, A.G.; Muggenburg, B.A.; Snipes, M.B.; De, Bice

doi:10.1126/science.4071052

Cited by 300 publications

(153 citation statements)

References 9 publications

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“…In the present study, 6 hr after instillation-an early time point not investigated before (Corry et al, 1984;Harmsen et al, 1985Harmsen et al, , 1987Havenith et al, 1993;Pabst and Binns, 1995)-donor lymphocytes were found in the draining lymph nodes, pointing to a rapid migratory capacity of bronchoalveolar lymphocytes once they have left the bronchoalveolar space with its suppressive effect on lymphocyte function (Kirby et al, 1985;Shimizu et al, 1988). Note that i.t.…”

Section: Discussionsupporting

confidence: 47%

“…The antigens entering the respiratory tract are cleared by the mucociliar system or phagocytized by cells of the unspecific lung immune system, e.g., alveolar macrophages, dendritic cells, or neutrophils, which have all been shown to leave the alveolar space, reenter the lung tissue, and migrate to regional lymph nodes, where the primary immune response can be initiated (Corry et al, 1984;Harmsen et al, 1985Harmsen et al, , 1987Havenith et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

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Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system

et al. 2001

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Lymphocytes in the bronchoalveolar space are routinely obtained and examined in lung diseases such as asthma or sarcoidosis. In a pig model, labeled lymphocytes were found in regional lymph nodes after intrabronchial instillation, indicating that reentry of lymphocytes from the bronchoalveaolar space into the body is possible. In the present study, the route and kinetics of the reentry of bronchoalveolar lymphocytes were investigated in a congenic rat model using immunohistochemistry on cryostat and semithin sections and confocal laser scanning microscopy. As early as 15 min after intratracheal instillation lymphocytes were found to leave the bronchoalveolar space by transmigration through alveolar but not bronchial epithelium and were observed in interstitial alveolar tissue. At 6 hr after intratracheal instillation, T and B lymphocytes appeared in the draining lymph nodes of the lung with an increase after 24 and 48 hr. The kinetic pattern clearly differed in nondraining lymph nodes and other organs. After 6 hr, only single cells were found in nondraining lymph nodes, spleen, and blood with a slight increase after 24 hr, and only occasionally were single cells seen in the liver, thymus, or Peyer's patches 24 and 48 hr after instillation. In conclusion, T and B lymphocytes can leave the alveolar space by reentry into the lung tissue through alveolar epithelium. They reach regional lymph nodes by means of lymphatic vessels and are then distributed all over the body to rejoin the systemic immune system. Coming into contact with environmental antigens, these lymphocytes could perform an important function in the lung immune system and might be a target for inhalative therapy. Anat Key words: pulmonary immune system; lung; lymphocytes; bronchoalveolar space; migration; bronchial lymph node; ratThe lungs are permanently in contact with the outside world and confronted with a large number of antigens and potentially harmful infectious agents. The lymphocytes of the pulmonary immune system are located in different lung compartments, e.g., the intravascular pool, the interstitial pool and the bronchoalveolar pool. They recognize foreign antigens specifically and activate the effector mechanisms that are required for host defense. These cells and their ability to migrate between the circulation, sites of antigen exposure, and lymphoid tissue are of critical importance for the generation of the immune response (Pabst and Tschernig, 1995). The complex system of lymphocyte recruitment and recirculation in the lung is still incompletely understood.

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Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system

et al. 2001

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“…In vivo studies have demonstrated that particles are trafficked from the site of injection to local lymph nodes by mononuclear phagocytes (7)(8)(9)(10). This suggests that particulate Ag/adjuvant formulations may act by targeting Ag to phagocytic APCs in vivo, resulting in more efficient presentation to T cells (10,11).…”

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confidence: 99%

Vesicle Size Influences the Trafficking, Processing, and Presentation of Antigens in Lipid Vesicles

Brewer

Pollock

Tetley

et al. 2004

The Journal of Immunology

120

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Although it is accepted that particulate Ags are more immunogenic than soluble Ags in vivo, it is unclear whether this effect can be explained solely through enhanced uptake by APCs. In this study we demonstrate that vesicle size modulated the efficiency of Ag presentation by murine macrophages and that this effect was accompanied by a profound change in trafficking of Ag. Ag prepared in large particles (560 nm) was delivered into early endosome-like, immature phagosomes, whereas smaller vesicles (155 nm) and soluble Ags localized rapidly to late endosomes/lysosomes. However, peptide/class II complexes could be detected in both compartments. Phagosomes formed on uptake of large vesicles recruit Ag-processing apparatus while retaining the characteristics of early endosomes. In contrast, smaller vesicles bypassed this compartment, appeared to go more rapidly to lysosomal compartments, and exhibited reduced Ag-presenting efficiency. We conclude that the ability of phagocytosed, particulate Ag to target early phagosomes results in more efficient Ag presentation.

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“…If this fails, the bacteria are able to escape death by entering the cytosol (van der Wel et al, 2007). TB-infected macrophages can travel to the hilar lymph nodes and bloodstream (Henderson et al, 1963;Harmsen et al, 1985) and this interaction is critical in the dissemination and systematic spread of the pathogen.…”

Section: The Host-pathogen Interaction and Adhesinsmentioning

confidence: 99%

Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

2014

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Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host’s defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host–pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

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The Role of Macrophages in Particle Translocation from Lungs to Lymph Nodes

Cited by 300 publications

References 9 publications

Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system

Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system

Vesicle Size Influences the Trafficking, Processing, and Presentation of Antigens in Lipid Vesicles

Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

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