Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Oct;149(4):1303–1312.

Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

E S Yi 1, H Lee 1, Y K Suh 1, W Tang 1, M Qi 1, S Yin 1, D G Remick 1, T R Ulich 1
PMCID: PMC1865196  PMID: 8863677

Abstract

Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.

Full text

PDF
1303

Images in this article

1305Figure 1
on p.1305
1305Figure 2
on p.1305
1306Figure 3
on p.1306
1306Figure 4
on p.1306
1306Figure 5
on p.1306
1306Figure 6
on p.1306
1308Figure 11
on p.1308
1309Figure 13
on p.1309
1309Figure 12
on p.1309
1310Figure 14
on p.1310

Selected References

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

  1. Amiri P., Locksley R. M., Parslow T. G., Sadick M., Rector E., Ritter D., McKerrow J. H. Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature. 1992 Apr 16;356(6370):604–607. doi: 10.1038/356604a0. [DOI] [PubMed] [Google Scholar]
  2. Chensue S. W., Terebuh P. D., Warmington K. S., Hershey S. D., Evanoff H. L., Kunkel S. L., Higashi G. I. Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function. J Immunol. 1992 Feb 1;148(3):900–906. [PubMed] [Google Scholar]
  3. Chensue S. W., Warmington K., Ruth J., Lincoln P., Kuo M. C., Kunkel S. L. Cytokine responses during mycobacterial and schistosomal antigen-induced pulmonary granuloma formation. Production of Th1 and Th2 cytokines and relative contribution of tumor necrosis factor. Am J Pathol. 1994 Nov;145(5):1105–1113. [PMC free article] [PubMed] [Google Scholar]
  4. Costabel U. The alveolitis of hypersensitivity pneumonitis. Eur Respir J. 1988 Jan;1(1):5–9. [PubMed] [Google Scholar]
  5. Davatelis G., Tekamp-Olson P., Wolpe S. D., Hermsen K., Luedke C., Gallegos C., Coit D., Merryweather J., Cerami A. Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokinetic properties. J Exp Med. 1988 Jun 1;167(6):1939–1944. doi: 10.1084/jem.167.6.1939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Denis M., Cormier Y., Fournier M., Tardif J., Laviolette M. Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model. Am J Respir Cell Mol Biol. 1991 Nov;5(5):477–483. doi: 10.1165/ajrcmb/5.5.477. [DOI] [PubMed] [Google Scholar]
  7. Denis M., Cormier Y., Laviolette M., Ghadirian E. T cells in hypersensitivity pneumonitis: effects of in vivo depletion of T cells in a mouse model. Am J Respir Cell Mol Biol. 1992 Feb;6(2):183–189. doi: 10.1165/ajrcmb/6.2.183. [DOI] [PubMed] [Google Scholar]
  8. Denis M., Cormier Y., Tardif J., Ghadirian E., Laviolette M. Hypersensitivity pneumonitis: whole Micropolyspora faeni or antigens thereof stimulate the release of proinflammatory cytokines from macrophages. Am J Respir Cell Mol Biol. 1991 Aug;5(2):198–203. doi: 10.1165/ajrcmb/5.2.198. [DOI] [PubMed] [Google Scholar]
  9. Dewald B., Moser B., Barella L., Schumacher C., Baggiolini M., Clark-Lewis I. IP-10, a gamma-interferon-inducible protein related to interleukin-8, lacks neutrophil activating properties. Immunol Lett. 1992 Mar;32(1):81–84. doi: 10.1016/0165-2478(92)90203-z. [DOI] [PubMed] [Google Scholar]
  10. Flory C. M., Jones M. L., Warren J. S. Pulmonary granuloma formation in the rat is partially dependent on monocyte chemoattractant protein 1. Lab Invest. 1993 Oct;69(4):396–404. [PubMed] [Google Scholar]
  11. Hill P. A., Lan H. Y., Nikolic-Paterson D. J., Atkins R. C. Pulmonary expression of ICAM-1 and LFA-1 in experimental Goodpasture's syndrome. Am J Pathol. 1994 Jul;145(1):220–227. [PMC free article] [PubMed] [Google Scholar]
  12. Huang S., Paulauskis J. D., Kobzik L. Rat KC cDNA cloning and mRNA expression in lung macrophages and fibroblasts. Biochem Biophys Res Commun. 1992 Apr 30;184(2):922–929. doi: 10.1016/0006-291x(92)90679-f. [DOI] [PubMed] [Google Scholar]
  13. Kaplan G., Luster A. D., Hancock G., Cohn Z. A. The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin. J Exp Med. 1987 Oct 1;166(4):1098–1108. doi: 10.1084/jem.166.4.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larsson K., Eklund A., Malmberg P., Bjermer L., Lundgren R., Belin L. Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis. Chest. 1992 Jan;101(1):109–114. doi: 10.1378/chest.101.1.109. [DOI] [PubMed] [Google Scholar]
  15. Lesley J., Hyman R., Kincade P. W. CD44 and its interaction with extracellular matrix. Adv Immunol. 1993;54:271–335. doi: 10.1016/s0065-2776(08)60537-4. [DOI] [PubMed] [Google Scholar]
  16. Lukacs N. W., Chensue S. W., Strieter R. M., Warmington K., Kunkel S. L. Inflammatory granuloma formation is mediated by TNF-alpha-inducible intercellular adhesion molecule-1. J Immunol. 1994 Jun 15;152(12):5883–5889. [PubMed] [Google Scholar]
  17. Lukacs N. W., Kunkel S. L., Strieter R. M., Warmington K., Chensue S. W. The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation. J Exp Med. 1993 Jun 1;177(6):1551–1559. doi: 10.1084/jem.177.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mochizuki I., Kobayashi T., Wada R., Kawaguchi T., Ozawa K., Fukushima M., Hirose Y., Kono H., Takeda J., Kusama S. Vascular lesions in the biopsied bronchus of patients with sarcoidosis changes of the endothelial cells in aggregation of eosinophils. Sarcoidosis. 1990 Mar;7(1):35–41. [PubMed] [Google Scholar]
  19. Mulligan M. S., Polley M. J., Bayer R. J., Nunn M. F., Paulson J. C., Ward P. A. Neutrophil-dependent acute lung injury. Requirement for P-selectin (GMP-140). J Clin Invest. 1992 Oct;90(4):1600–1607. doi: 10.1172/JCI116029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mulligan M. S., Varani J., Dame M. K., Lane C. L., Smith C. W., Anderson D. C., Ward P. A. Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J Clin Invest. 1991 Oct;88(4):1396–1406. doi: 10.1172/JCI115446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ohmori Y., Hamilton T. A. A macrophage LPS-inducible early gene encodes the murine homologue of IP-10. Biochem Biophys Res Commun. 1990 May 16;168(3):1261–1267. doi: 10.1016/0006-291x(90)91164-n. [DOI] [PubMed] [Google Scholar]
  22. Rosen Y., Moon S., Huang C. T., Gourin A., Lyons H. A. Granulomatous pulmonary angiitis in sarcoidosis. Arch Pathol Lab Med. 1977 Apr;101(4):170–174. [PubMed] [Google Scholar]
  23. Schuyler M., Gott K., Edwards B., Nikula K. J. Experimental hypersensitivity pneumonitis. Effect of CD4 cell depletion. Am J Respir Crit Care Med. 1994 May;149(5):1286–1294. doi: 10.1164/ajrccm.149.5.7909706. [DOI] [PubMed] [Google Scholar]
  24. Schuyler M., Gott K., Haley P. Experimental murine hypersensitivity pneumonitis. Cell Immunol. 1991 Sep;136(2):303–317. doi: 10.1016/0008-8749(91)90354-e. [DOI] [PubMed] [Google Scholar]
  25. Seal R. M., Hapke E. J., Thomas G. O., Meek J. C., Hayes M. The pathology of the acute and chronic stages of farmer's lung. Thorax. 1968 Sep;23(5):469–489. doi: 10.1136/thx.23.5.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Takemura T., Matsui Y., Oritsu M., Akiyama O., Hiraga Y., Omichi M., Hirasawa M., Saiki S., Tamura S., Mochizuki I. Pulmonary vascular involvement in sarcoidosis: granulomatous angiitis and microangiopathy in transbronchial lung biopsies. Virchows Arch A Pathol Anat Histopathol. 1991;418(4):361–368. doi: 10.1007/BF01600167. [DOI] [PubMed] [Google Scholar]
  27. Taub D. D., Lloyd A. R., Conlon K., Wang J. M., Ortaldo J. R., Harada A., Matsushima K., Kelvin D. J., Oppenheim J. J. Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med. 1993 Jun 1;177(6):1809–1814. doi: 10.1084/jem.177.6.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ulich T. R., Guo K. Z., Remick D., del Castillo J., Yin S. M. Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6. J Immunol. 1991 Apr 1;146(7):2316–2323. [PubMed] [Google Scholar]
  30. Ulich T. R., Watson L. R., Yin S. M., Guo K. Z., Wang P., Thang H., del Castillo J. The intratracheal administration of endotoxin and cytokines. I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate. Am J Pathol. 1991 Jun;138(6):1485–1496. [PMC free article] [PubMed] [Google Scholar]
  31. Wegner C. D., Wolyniec W. W., LaPlante A. M., Marschman K., Lubbe K., Haynes N., Rothlein R., Letts L. G. Intercellular adhesion molecule-1 contributes to pulmonary oxygen toxicity in mice: role of leukocytes revised. Lung. 1992;170(5):267–279. doi: 10.1007/BF00566679. [DOI] [PubMed] [Google Scholar]
  32. Yoshimura T., Takeya M., Takahashi K. Molecular cloning of rat monocyte chemoattractant protein-1 (MCP-1) and its expression in rat spleen cells and tumor cell lines. Biochem Biophys Res Commun. 1991 Jan 31;174(2):504–509. doi: 10.1016/0006-291x(91)91445-i. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES