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Characterization of murine lung interstitial macrophages in comparison with alveolar macrophages in vitro
Abstract
The present study was performed to characterize the immunologic potential of interstitial macrophages (INT) in comparison with alveolar macrophages (AL). The data showed that AL, compared with INT, have a more efficient phagocytic potential. In addition, they have a strong microbicidal activity and secrete large amounts of reactive oxygen radicals, nitric oxides, TNF, and IFN on appropriate stimulation. They also exert strong tumoricidal and parasiticidal activities. In contrast, INT are more efficient in releasing immunoregulatory cytokines such as IL-1 and IL-6. As determined by Ab staining, INT express more MHC class II molecules and are more effective in functioning as accessory cells for mitogen-stimulated lymphocyte proliferation compared with AL. Thus, AL appear to be particularly effective as nonspecific first line defense cells against infectious agents, whereas INT are equipped to cooperate with interstitial lymphocytes in inducing a specific immune reaction.
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“Among host innate immune players, resident alveolar macrophages (AMs) are considered to be the most important first line of defense against respiratory pneumococcal infections (13), through their high phagocytic capacity (14–16).”
From Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections (2013) · cites this paper as [14]
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“6 4 The activated macrophages would then secrete reactive oxygen species, nitric oxides, and inflammatory cytokines, with the alveolar macrophages secreting more of the radical molecules and TNF and the interstit ial macrophages releasing more of the inflammatory cytokines Il-1 and IL-6.(65) ROS attack on membrane lip…”
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An Overview of Reactive Oxygen Species
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“Under steady-state, two distinct populations of macrophages, the interstitial macrophages (IMs) and alveolar macrophages (AMs), are present in the lungs (48, 49).”
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Draijer, C., Penke, L. R. K., & Peters-Golden, M. L. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801387 · Cited by 60
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“However, the percentage of AM contaminations in IM preparations obtained by similar methods in the rat and mouse system was below 5% (8), which is not sufficient to explain the functional heterogeneity between the two macrophage populations.”
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“In this context, a lower phagocytosis capacity of yeast (S. cerevisiae) has been described for IM compared to AM (Franke-Ullmann et al. 1996).”
Aerobiology and Inhalation Exposure to Biological Select Agents and Toxins
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“Some evidence suggests, however, that they may in fact act like other macrophages as professional antigen-presenting cells.(18,33) Interstitial DCs are found throughout the lungs and upper respiratory tract.”
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“Macrophages are within the first cells that protect the host against the viral infection, and there are two types in the lungs: the alveolar macrophages (AMs) and the interstitial macrophages (IMs) [138].”
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“The predominance and contribution of different macrophage subpopulations to the immunopathogenesis of COPD is unclear, especially given the complexity and diversity that entails themacrophage population [34,35].”
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“This heterogeneity results in a population of cells with variable immune function (15).”
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“In contrast, there are numerous reports that alveolar macrophages have greater functional activity related to antimicrobial defense, including phagocytosis, compared to interstitial macrophages which display enhanced capabilities relevant to specific immune responses such as antigen processing as well as in antioxidan…”
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“reactive oxygen intermediates, nitric oxide (NO), TNF-a and interferons following stimulation.(71) Macrophages also contribute to immune responses by releasing IL-1 and IL-6, and by upregulating MHC molecules to more efficiently present antigen to recruited lymphocytes.”
BackgroundPlasticity towards Rigidity: A Macrophage Conundrum in Pulmonary Fibrosis
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Ahn, J., Park, J., Kim, D., Lee, T., Jung, D., Kim, Y.-J., Lee, Y., Lee, Y., Seo, I.-S., Song, E., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.738070 · Cited by 24
“(D) AMs were incubated with MAB (MOI 1:25) and indicated reagents (2 h pretreated, L-NAME 1 mM, rIFN-b 1,000 units/ml).”
BackgroundInfluentialMitochondrial Regulation of Inflammasome Activation in Chronic Obstructive Pulmonary Disease
Yoon, C. M., Nam, M., Oh, Y., Cruz, C. S. D., & Kang, M. (2015) · Journal of Innate Immunity · doi:10.1159/000441299 · Cited by 23
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“Pig and mouse alveolar macrophages are known to have potent phagocytic abilities and to be good sources of cytokine production, including IL-1, TNF-K, and IFN-Q [5,26,27].”
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Phenotypic and Functional Heterogeneity of Low-Density and High-Density Human Lung Macrophages
Balestrieri, B., Granata, F., Loffredo, S., Petraroli, A., Scalia, G., Morabito, P., Cardamone, C., Varricchi, G., & Triggiani, M. (2021) · Biomedicines · doi:10.3390/biomedicines9050505 · Cited by 23
“Differences in morphology, phenotype and function between alveolar and interstitial macrophages in rodents [42,43] and in humans [22,27] have been reported.”
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Heterogeneity of Lung Mononuclear Phagocytes in Chronic Obstructive Pulmonary Disease
Lee, J. S. (2012) · Journal of Innate Immunity · doi:10.1159/000337434 · Cited by 21
Rodriguez-Rodriguez, L., Gillet, L., & Machiels, B. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1149015 · Cited by 23
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In situ immune responses to interstitial pneumonitis in human visceral leishmaniasis
Tuon, F. F., Guedes, F., Fernandes, E. R., Pagliari, C., Amato, V. S., & Duarte, M. I. S. (2008) · Parasite Immunology · doi:10.1111/j.1365-3024.2008.01080.x · Cited by 18
McCubbrey, A. L., Barthel, L., Mould, K. J., Mohning, M. P., Redente, E. F., & Janssen, W. J. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00141.2016 · Cited by 17
Li, M., Li, J., Wang, Y., Jiang, G., Jiang, H., Li, M., Zhu, Z., Ren, F., Wang, Y., Yan, M., et al. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-04091-7 · Cited by 17
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Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages
Immanuel, C. N., Teng, B., Dong, B. E., Gordon, E. M., Kennedy, J. A., Luellen, C. L., Schwingshackl, A., Cormier, S. A., Fitzpatrick, E. A., & Waters, C. M. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00199.2018 · Cited by 18
“Macrophages were isolated by consecutive bronchoalveolar lavage as previously described (7, 43, 52, 55) with some minor modifications indicated below.”
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Harpur, C. M., Page, M. A. L., & Tate, M. D. (2021) · Virulence · doi:10.1080/21505594.2021.1939608 · Cited by 16
“IM can be distinguished from AM by their lack of CD11c expression [79] and are generally less phagocytic but more effective at stimulating T cell proliferation [77,80].”
BackgroundLineage tracing reveals the origins and dynamics of macrophages in lung injury and repair
Jin, H., Mou, J., Zhu, H., Liu, K., Zhang, M., Zhang, Z., Pflanz, S., Kasmi, K. E., Liu, Z., Ginhoux, F., et al. (2026) · Cell Discovery · doi:10.1038/s41421-025-00859-0 · Cited by 17
“In contrast, IMs are predominantly found in the lung parenchyma and express high levels of CD11b 16,18 .”
Neuroendocrine and immune interactions with airway macrophages
James, D., & Nijkamp, F. P. (2000) · Inflammation Research · doi:10.1007/pl00000205 · Cited by 12
Yang, S., Zeng, J., Hao, W., Sun, R., Tuo, Y., Tan, L., Zhang, H., Liu, R., & Bai, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612557 · Cited by 13
Metadata
- Authors
- Franke-Ullmann, G., Pförtner, C., Walter, P., Steinmüller, C., Lohmann-Matthes, M. L., & Kobzik, L.
- Affiliations
- Fraunhofer Institute for Toxicology and Experimental Medicine (DE)
- ORCID
- Kobzik, L
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-10-01
- Volume
- 157
- Issue
- 7
- Pages
- 3097-3104
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1539936851
- Cited by
- 160
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 12 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 10 · 2014: 7 · 2013: 12 · 2012: 5
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- interstitial macrophages, alveolar macrophages, lung macrophages, phagocytosis, microbicidal activity, reactive oxygen radicals, nitric oxide, TNF-α, interferon, immunoregulatory cytokines, MHC class II, accessory cells, lymphocyte proliferation, innate immunity, adaptive immunity, mouse lung
- MeSH terms
- Interleukin-6 Inhibitors, Animals, Antigen-Presenting Cells, Cells, Cultured, Female, Interferons, Interleukin-1, L Cells, Leishmania donovani, Lung, Macrophage Activation, Macrophages, Mice, Inbred BALB C, Phagocytosis, Mast-Cell Sarcoma, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Interleukin-6, Macrophages, Alveolar, Reactive Oxygen Species, Mice
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