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. 1996 Feb;148(2):657–666.

Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity.

J A MacLean 1, W Xia 1, C E Pinto 1, L Zhao 1, H W Liu 1, R L Kradin 1
PMCID: PMC1861667  PMID: 8579128

Abstract

Dendritic cells (DCs) have emerged as the dominant antigen-presenting cells (APCs) of the lung, playing a vital role in the induction of cell-mediated immunity to inhaled antigens. We have previously demonstrated that an airway challenge with the soluble antigen hen egg lysozyme yields rapid acquisition of specific antigen-presenting cell activity by purified pulmonary DCs and a cell-mediated immune response in the lung upon secondary challenge. To examine how a particulate antigen leads to a cell-mediated response in vivo, graded concentrations of heat-killed Listeria (HKL) were injected intratracheally into Lewis rats. The bacteria were rapidly ingested by lung macrophages and polymorphonuclear leukocytes. The ability of purified pulmonary DCs pulsed in vivo by an airway challenge with HKL to subsequently stimulate HKL-specific responses ex vivo showed a threshold response, requiring a dose in excess of 10(9) organisms/rat. By contrast, all dosages of HKL yielded specific sensitization of lymphocytes in the draining bilar nodes. Pulmonary DCs purified from rats after a secondary in vivo airway challenge with HKL at day 14 were ineffective antigen-presenting cells except at high dosages of antigen. The generation of cell-mediated pulmonary inflammation paralleled the antigen-presenting cell activity of pulmonary DCs and was observed only at high antigen dosages. Hen egg lysozyme immobilized onto polystyrene beads and injected intratracheally yielded comparable results to those observed with HKL. We suggest that a pulmonary cellular immune response is generated to an inhaled particulate antigen when the protective phagocytic capacities of the lung are exceeded and antigen is able to interact directly with interstitial DCs. The diversion of particulate antigens by pulmonary phagocytes may help to limit undesirable pulmonary inflammation while allowing the generation of antigen-specific immune lymphocytes in vivo.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Corry D., Kulkarni P., Lipscomb M. F. The migration of bronchoalveolar macrophages into hilar lymph nodes. Am J Pathol. 1984 Jun;115(3):321–328. [PMC free article] [PubMed] [Google Scholar]
  2. Crowley M., Inaba K., Steinman R. M. Dendritic cells are the principal cells in mouse spleen bearing immunogenic fragments of foreign proteins. J Exp Med. 1990 Jul 1;172(1):383–386. doi: 10.1084/jem.172.1.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Drevets D. A., Campbell P. A. Macrophage phagocytosis: use of fluorescence microscopy to distinguish between extracellular and intracellular bacteria. J Immunol Methods. 1991 Aug 28;142(1):31–38. doi: 10.1016/0022-1759(91)90289-r. [DOI] [PubMed] [Google Scholar]
  4. Gong J. L., McCarthy K. M., Rogers R. A., Schneeberger E. E. Interstitial lung macrophages interact with dendritic cells to present antigenic peptides derived from particulate antigens to T cells. Immunology. 1994 Mar;81(3):343–351. [PMC free article] [PubMed] [Google Scholar]
  5. Gong J. L., McCarthy K. M., Telford J., Tamatani T., Miyasaka M., Schneeberger E. E. Intraepithelial airway dendritic cells: a distinct subset of pulmonary dendritic cells obtained by microdissection. J Exp Med. 1992 Mar 1;175(3):797–807. doi: 10.1084/jem.175.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Havenith C. E., Breedijk A. J., Hoefsmit E. C. Effect of Bacillus Calmette-Guérin inoculation on numbers of dendritic cells in bronchoalveolar lavages of rats. Immunobiology. 1992 Apr;184(4-5):336–347. doi: 10.1016/S0171-2985(11)80591-7. [DOI] [PubMed] [Google Scholar]
  8. Havenith C. E., van Miert P. P., Breedijk A. J., Beelen R. H., Hoefsmit E. C. Migration of dendritic cells into the draining lymph nodes of the lung after intratracheal instillation. Am J Respir Cell Mol Biol. 1993 Nov;9(5):484–488. doi: 10.1165/ajrcmb/9.5.484. [DOI] [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., Oliver J., Bilyk N., McMenamin C., McMenamin P. G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993 Feb 1;177(2):397–407. doi: 10.1084/jem.177.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Holt P. G. Regulation of antigen-presenting cell function(s) in lung and airway tissues. Eur Respir J. 1993 Jan;6(1):120–129. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Inaba K., Inaba M., Naito M., Steinman R. M. Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo. J Exp Med. 1993 Aug 1;178(2):479–488. doi: 10.1084/jem.178.2.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. King P. D., Katz D. R. Mechanisms of dendritic cell function. Immunol Today. 1990 Jun;11(6):206–211. doi: 10.1016/0167-5699(90)90084-m. [DOI] [PubMed] [Google Scholar]
  16. Klinkert W. E., LaBadie J. H., Bowers W. E. Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues. J Exp Med. 1982 Jul 1;156(1):1–19. doi: 10.1084/jem.156.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kradin R. L., McCarthy K. M., Dailey C. I., Burdeshaw A., Kurnick J. T., Schneeberger E. E. The poor accessory cell function of macrophages in the rat may reflect their inability to form clusters with T cells. Clin Immunol Immunopathol. 1987 Sep;44(3):348–363. doi: 10.1016/0090-1229(87)90079-1. [DOI] [PubMed] [Google Scholar]
  18. Kradin R. L., McCarthy K. M., Gifford J., Schneeberger E. E. Antigen-independent binding of T-cells by dendritic cells and alveolar macrophages in the rat. Am Rev Respir Dis. 1989 Jan;139(1):207–211. doi: 10.1164/ajrccm/139.1.207. [DOI] [PubMed] [Google Scholar]
  19. Kradin R. L., McCarthy K. M., Xia W. J., Lazarus D., Schneeberger E. E. Accessory cells of the lung. I. Interferon-gamma increases Ia+ dendritic cells in the lung without augmenting their accessory activities. Am J Respir Cell Mol Biol. 1991 Mar;4(3):210–218. doi: 10.1165/ajrcmb/4.3.210. [DOI] [PubMed] [Google Scholar]
  20. Lipscomb M. F., Huffnagle G. B., Lovchik J. A., Lyons C. R., Pollard A. M., Yates J. L. The role of T lymphocytes in pulmonary microbial defense mechanisms. Arch Pathol Lab Med. 1993 Dec;117(12):1225–1232. [PubMed] [Google Scholar]
  21. McWilliam A. S., Nelson D., Thomas J. A., Holt P. G. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J Exp Med. 1994 Apr 1;179(4):1331–1336. doi: 10.1084/jem.179.4.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pollard A. M., Lipscomb M. F. Characterization of murine lung dendritic cells: similarities to Langerhans cells and thymic dendritic cells. J Exp Med. 1990 Jul 1;172(1):159–167. doi: 10.1084/jem.172.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reis e Sousa C., Stahl P. D., Austyn J. M. Phagocytosis of antigens by Langerhans cells in vitro. J Exp Med. 1993 Aug 1;178(2):509–519. doi: 10.1084/jem.178.2.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schon-Hegrad M. A., Oliver J., McMenamin P. G., Holt P. G. Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (Ia)-bearing dendritic cells (DC) in the conducting airways. J Exp Med. 1991 Jun 1;173(6):1345–1356. doi: 10.1084/jem.173.6.1345. [DOI] [PMC free article] [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. Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974 Feb 1;139(2):380–397. doi: 10.1084/jem.139.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
  28. Steinman R. M., Witmer-Pack M., Inaba K. Dendritic cells: antigen presentation, accessory function and clinical relevance. Adv Exp Med Biol. 1993;329:1–9. doi: 10.1007/978-1-4615-2930-9_1. [DOI] [PubMed] [Google Scholar]
  29. Thepen T., Claassen E., Hoeben K., Brevé J., Kraal G. Migration of alveolar macrophages from alveolar space to paracortical T cell area of the draining lymph node. Adv Exp Med Biol. 1993;329:305–310. doi: 10.1007/978-1-4615-2930-9_51. [DOI] [PubMed] [Google Scholar]
  30. Toews G. B., Vial W. C., Dunn M. M., Guzzetta P., Nunez G., Stastny P., Lipscomb M. F. The accessory cell function of human alveolar macrophages in specific T cell proliferation. J Immunol. 1984 Jan;132(1):181–186. [PubMed] [Google Scholar]
  31. Xia W. J., Schneeberger E. E., McCarthy K., Kradin R. L. Accessory cells of the lung. II. Ia+ pulmonary dendritic cells display cell surface antigen heterogeneity. Am J Respir Cell Mol Biol. 1991 Sep;5(3):276–283. doi: 10.1165/ajrcmb/5.3.276. [DOI] [PubMed] [Google Scholar]
  32. Xia W., Pinto C. E., Kradin R. L. The antigen-presenting activities of Ia+ dendritic cells shift dynamically from lung to lymph node after an airway challenge with soluble antigen. J Exp Med. 1995 Apr 1;181(4):1275–1283. doi: 10.1084/jem.181.4.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]

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