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. 1989 Aug 1;170(2):499–509. doi: 10.1084/jem.170.2.499

Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice

PMCID: PMC2189410  PMID: 2526847

Abstract

A single intracheal dose of liposome-encapsuled dichloro-methylene- diphosphonate resulted in the elimination of alveolar macrophages (AM) from the lung, creating a model to study the in vivo role of AM in the pulmonary immune response. Using intratracheally administered trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH), the kinetics of the response, the location and number of TNP-specific antibody-forming cells, and the different Ig classes of the antibodies produced were studied in AM-depleted animals. The results show that AM elimination has a dramatic effect on the pulmonary immune responses against TNP- KLH. An increase in APC in lung-associated lymph nodes and a prolongation of the response is found, as well as an introduction of APC in lung tissue. In both experimental groups, the majority of the TNP-specific antibodies produced was IgG, followed by IgA and IgE, while very few IgM antibodies could be detected. We conclude from these results that AM are likely to play a role in controlling the pulmonary immune response in a suppressive way, thereby limiting the possible damage caused by severe immune responses in lung tissue.

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Selected References

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  1. BURSTONE M. S. Histochemical comparison of naphthol AS-phosphates for the demonstration of phosphatases. J Natl Cancer Inst. 1958 Mar;20(3):601–615. [PubMed] [Google Scholar]
  2. Bice D. E., Shopp G. M. Antibody responses after lung immunization. Exp Lung Res. 1988;14(2):133–155. doi: 10.3109/01902148809115121. [DOI] [PubMed] [Google Scholar]
  3. Brain J. D. Lung macrophages: how many kinds are there? What do they do? Am Rev Respir Dis. 1988 Mar;137(3):507–509. doi: 10.1164/ajrccm/137.3.507. [DOI] [PubMed] [Google Scholar]
  4. Breel M., Van der Ende M., Sminia T., Kraal G. Subpopulations of lymphoid and non-lymphoid cells in bronchus-associated lymphoid tissue (BALT) of the mouse. Immunology. 1988 Apr;63(4):657–662. [PMC free article] [PubMed] [Google Scholar]
  5. Claassen E., Van Rooijen N. TNP-enzyme conjugates for the detection of anti-TNP antibody producing cells in vivo. J Immunol Methods. 1984 Dec 14;75(1):181–188. doi: 10.1016/0022-1759(84)90237-0. [DOI] [PubMed] [Google Scholar]
  6. Harmsen A. G., Mason M. J., Muggenburg B. A., Gillett N. A., Jarpe M. A., Bice D. E. Migration of neutrophils from lung to tracheobronchial lymph node. J Leukoc Biol. 1987 Feb;41(2):95–103. doi: 10.1002/jlb.41.2.95. [DOI] [PubMed] [Google Scholar]
  7. Harmsen A. G., Muggenburg B. A., Snipes M. B., Bice D. E. The role of macrophages in particle translocation from lungs to lymph nodes. Science. 1985 Dec 13;230(4731):1277–1280. doi: 10.1126/science.4071052. [DOI] [PubMed] [Google Scholar]
  8. Holt P. G., Degebrodt A., O'Leary C., Krska K., Plozza T. T cell activation by antigen-presenting cells from lung tissue digests: suppression by endogenous macrophages. Clin Exp Immunol. 1985 Dec;62(3):586–593. [PMC free article] [PubMed] [Google Scholar]
  9. Holt P. G. Down-regulation of immune responses in the lower respiratory tract: the role of alveolar macrophages. Clin Exp Immunol. 1986 Feb;63(2):261–270. [PMC free article] [PubMed] [Google Scholar]
  10. Holt P. G., Schon-Hegrad M. A. Localization of T cells, macrophages and dendritic cells in rat respiratory tract tissue: implications for immune function studies. Immunology. 1987 Nov;62(3):349–356. [PMC free article] [PubMed] [Google Scholar]
  11. Holt P. G., Schon-Hegrad M. A., Oliver J. MHC class II antigen-bearing dendritic cells in pulmonary tissues of the rat. Regulation of antigen presentation activity by endogenous macrophage populations. J Exp Med. 1988 Feb 1;167(2):262–274. doi: 10.1084/jem.167.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hunninghake G. W. Immunoregulatory functions of human alveolar macrophages. Am Rev Respir Dis. 1987 Aug;136(2):253–254. doi: 10.1164/ajrccm/136.2.253. [DOI] [PubMed] [Google Scholar]
  13. Kaltreider H. B., Curtis J. L., Arraj S. M. The mechanism of appearance of specific antibody-forming cells in lungs of inbred mice after immunization with sheep erythrocytes intratracheally. II. Dose-dependence and kinetics of appearance of antibody-forming cells in hilar lymph nodes and lungs of unprimed and primed mice. Am Rev Respir Dis. 1987 Jan;135(1):87–92. doi: 10.1164/arrd.1987.135.1.87. [DOI] [PubMed] [Google Scholar]
  14. Kraal G., Rep M., Janse M. Macrophages in T and B cell compartments and other tissue macrophages recognized by monoclonal antibody MOMA-2. An immunohistochemical study. Scand J Immunol. 1987 Dec;26(6):653–661. doi: 10.1111/j.1365-3083.1987.tb02301.x. [DOI] [PubMed] [Google Scholar]
  15. Lehnert B. E., Valdez Y. E., Stewart C. C. Translocation of particles to the tracheobronchial lymph nodes after lung deposition: kinetics and particle-cell relationships. Exp Lung Res. 1986;10(3):245–266. doi: 10.3109/01902148609061496. [DOI] [PubMed] [Google Scholar]
  16. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  17. Monick M., Glazier J., Hunninghake G. W. Human alveolar macrophages suppress interleukin-1 (IL-1) activity via the secretion of prostaglandin E2. Am Rev Respir Dis. 1987 Jan;135(1):72–77. doi: 10.1164/arrd.1987.135.1.72. [DOI] [PubMed] [Google Scholar]
  18. Naor D., Morecki S., Mitchell G. F. Differential induction of anti-trinitrophenyl plaque-forming cell responses to lightly and heavily conjugated trinitrophenylated heterologous and autologous erythrocytes in mice. Eur J Immunol. 1974 Apr;4(4):311–314. doi: 10.1002/eji.1830040415. [DOI] [PubMed] [Google Scholar]
  19. Nuntirooj K., Bozelka B. E., deShazo R. D., Salvaggio J. E. Analytical and functional assessment of lymphoid cells within murine lung. Exp Lung Res. 1987;13(1):13–24. doi: 10.3109/01902148709064306. [DOI] [PubMed] [Google Scholar]
  20. Pabst R., Binns R. M., Licence S. T., Peter M. Evidence of a selective major vascular marginal pool of lymphocytes in the lung. Am Rev Respir Dis. 1987 Nov;136(5):1213–1218. doi: 10.1164/ajrccm/136.5.1213. [DOI] [PubMed] [Google Scholar]
  21. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  22. Rochester C. L., Goodell E. M., Stoltenborg J. K., Bowers W. E. Dendritic cells from rat lung are potent accessory cells. Am Rev Respir Dis. 1988 Jul;138(1):121–128. doi: 10.1164/ajrccm/138.1.121. [DOI] [PubMed] [Google Scholar]
  23. Saltini C., Hemler M. E., Crystal R. G. T lymphocytes compartmentalized on the epithelial surface of the lower respiratory tract express the very late activation antigen complex VLA-1. Clin Immunol Immunopathol. 1988 Feb;46(2):221–233. doi: 10.1016/0090-1229(88)90185-7. [DOI] [PubMed] [Google Scholar]
  24. Sedgwick J. D., Holt P. G. Induction of IgE-secreting cells and IgE isotype-specific suppressor T cells in the respiratory lymph nodes of rats in response to antigen inhalation. Cell Immunol. 1985 Aug;94(1):182–194. doi: 10.1016/0008-8749(85)90095-4. [DOI] [PubMed] [Google Scholar]
  25. Sertl K., Takemura T., Tschachler E., Ferrans V. J., Kaliner M. A., Shevach E. M. Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura. J Exp Med. 1986 Feb 1;163(2):436–451. doi: 10.1084/jem.163.2.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. van Rooijen N., van Nieuwmegen R. Elimination of phagocytic cells in the spleen after intravenous injection of liposome-encapsulated dichloromethylene diphosphonate. An enzyme-histochemical study. Cell Tissue Res. 1984;238(2):355–358. doi: 10.1007/BF00217308. [DOI] [PubMed] [Google Scholar]
  27. van der Brugge-Gamelkoorn G. J., Dijkstra C. D., Sminia T. Characterization of pulmonary macrophages and bronchus-associated lymphoid tissue (BALT) macrophages in the rat. An enzyme-cytochemical and immunocytochemical study. Immunobiology. 1985 Jul;169(5):553–562. doi: 10.1016/S0171-2985(85)80009-7. [DOI] [PubMed] [Google Scholar]
  28. van oud Alblas A. B., van Furth R. Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state. J Exp Med. 1979 Jun 1;149(6):1504–1518. doi: 10.1084/jem.149.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]

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