Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Jun;65(6):2278–2282. doi: 10.1128/iai.65.6.2278-2282.1997

Depletion of alveolar macrophages exacerbates respiratory mycoplasmosis in mycoplasma-resistant C57BL mice but not mycoplasma-susceptible C3H mice.

J M Hickman-Davis 1, S M Michalek 1, J Gibbs-Erwin 1, J R Lindsey 1
PMCID: PMC175316  PMID: 9169764

Abstract

Indirect evidence suggests that innate immune mechanisms involving alveolar macrophages (AMs) are of major importance in antimycoplasmal defense. We compared the effects of AM depletion on intrapulmonary killing of Mycoplasma pulmonis during the early phase of infection in mycoplasma-resistant C57BL/6NCr (C57BL) and mycoplasma-susceptible C3H/HeNCr (C3H) mice. More than 80% of AMs were depleted in both strains of mice by intratracheal insufflation of liposome-encapsulated dichloromethylene bisphosphonate (L-Cl2MBP), compared to no significant AM depletion in either strain following insufflation of liposome-encapsulated phosphate-buffered saline (L-PBS), PBS alone, or no treatment. AM-depleted (L-Cl2MBP) and control (L-PBS) mice were infected intranasally with 10(5) CFU of M. pulmonis UAB CT, and their lungs were quantitatively cultured to assess intrapulmonary killing at 0, 8, 12, and 48 h postinfection. AM depletion exacerbated the infection in C57BL mice by reducing killing of the organism to a level comparable to that in C3H mice without AM depletion. In contrast, AM depletion did not alter killing in C3H mice. These results directly identify the AM as the main effector cell in early pulmonary antimycoplasmal defense and suggest that differences in mycoplasmal killing by AMs may explain the resistance of C57BL mice and the susceptibility of C3H mice to mycoplasmal infection.

Full Text

The Full Text of this article is available as a PDF (154.8 KB).

Selected References

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

  1. Berg J. T., Lee S. T., Thepen T., Lee C. Y., Tsan M. F. Depletion of alveolar macrophages by liposome-encapsulated dichloromethylene diphosphonate. J Appl Physiol (1985) 1993 Jun;74(6):2812–2819. doi: 10.1152/jappl.1993.74.6.2812. [DOI] [PubMed] [Google Scholar]
  2. Bette M., Schäfer M. K., van Rooijen N., Weihe E., Fleischer B. Distribution and kinetics of superantigen-induced cytokine gene expression in mouse spleen. J Exp Med. 1993 Nov 1;178(5):1531–1539. doi: 10.1084/jem.178.5.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buiting A. M., Van Rooijen N. Liposome mediated depletion of macrophages: an approach for fundamental studies. J Drug Target. 1994;2(5):357–362. doi: 10.3109/10611869408996810. [DOI] [PubMed] [Google Scholar]
  4. Cartner S. C., Simecka J. W., Lindsey J. R., Cassell G. H., Davis J. K. Chronic respiratory mycoplasmosis in C3H/HeN and C57BL/6N mice: lesion severity and antibody response. Infect Immun. 1995 Oct;63(10):4138–4142. doi: 10.1128/iai.63.10.4138-4142.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Classen E., Van Rooijen N. Preparation and characteristics of dichloromethylene diphosphonate-containing liposomes. J Microencapsul. 1986 Apr-Jun;3(2):109–114. doi: 10.3109/02652048609031565. [DOI] [PubMed] [Google Scholar]
  6. Clyde W. A., Jr Mycoplasma pneumoniae respiratory disease symposium: summation and significance. Yale J Biol Med. 1983 Sep-Dec;56(5-6):523–527. [PMC free article] [PubMed] [Google Scholar]
  7. Dave J., Patel H. M. Differentiation in hepatic and splenic phagocytic activity during reticuloendothelial blockade with cholesterol-free and cholesterol-rich liposomes. Biochim Biophys Acta. 1986 Sep 19;888(2):184–190. doi: 10.1016/0167-4889(86)90020-0. [DOI] [PubMed] [Google Scholar]
  8. Davidson M. K., Lindsey J. R., Parker R. F., Tully J. G., Cassell G. H. Differences in virulence for mice among strains of Mycoplasma pulmonis. Infect Immun. 1988 Aug;56(8):2156–2162. doi: 10.1128/iai.56.8.2156-2162.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis J. K., Davidson M. K., Schoeb T. R., Lindsey J. R. Decreased intrapulmonary killing of Mycoplasma pulmonis after short-term exposure to NO2 is associated with damaged alveolar macrophages. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):406–411. doi: 10.1164/ajrccm/145.2_Pt_1.406. [DOI] [PubMed] [Google Scholar]
  10. Davis J. K., Delozier K. M., Asa D. K., Minion F. C., Cassell G. H. Interactions between murine alveolar macrophages and Mycoplasma pulmonis in vitro. Infect Immun. 1980 Aug;29(2):590–599. doi: 10.1128/iai.29.2.590-599.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davis J. K., Parker R. F., White H., Dziedzic D., Taylor G., Davidson M. K., Cox N. R., Cassell G. H. Strain differences in susceptibility to murine respiratory mycoplasmosis in C57BL/6 and C3H/HeN mice. Infect Immun. 1985 Dec;50(3):647–654. doi: 10.1128/iai.50.3.647-654.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Evengård B., Sandstedt K., Bölske G., Feinstein R., Riesenfelt-Orn I., Smith C. I. Intranasal inoculation of Mycoplasma pulmonis in mice with severe combined immunodeficiency (SCID) causes a wasting disease with grave arthritis. Clin Exp Immunol. 1994 Dec;98(3):388–394. doi: 10.1111/j.1365-2249.1994.tb05502.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Faulkner C. B., Simecka J. W., Davidson M. K., Davis J. K., Schoeb T. R., Lindsey J. R., Everson M. P. Gene expression and production of tumor necrosis factor alpha, interleukin 1, interleukin 6, and gamma interferon in C3H/HeN and C57BL/6N mice in acute Mycoplasma pulmonis disease. Infect Immun. 1995 Oct;63(10):4084–4090. doi: 10.1128/iai.63.10.4084-4090.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fleisch H. Bisphosphonates: a new class of drugs in diseases of bone and calcium metabolism. Recent Results Cancer Res. 1989;116:1–28. doi: 10.1007/978-3-642-83668-8_1. [DOI] [PubMed] [Google Scholar]
  15. Foy H. M. Infections caused by Mycoplasma pneumoniae and possible carrier state in different populations of patients. Clin Infect Dis. 1993 Aug;17 (Suppl 1):S37–S46. doi: 10.1093/clinids/17.supplement_1.s37. [DOI] [PubMed] [Google Scholar]
  16. Gnarpe J., Lundbäck A., Sundelöf B., Gnarpe H. Prevalence of Mycoplasma pneumoniae in subjectively healthy individuals. Scand J Infect Dis. 1992;24(2):161–164. doi: 10.3109/00365549209052607. [DOI] [PubMed] [Google Scholar]
  17. Hatch G. E., Slade R., Selgrade M. K., Stead A. G. Nitrogen dioxide exposure and lung antioxidants in ascorbic acid-deficient guinea pigs. Toxicol Appl Pharmacol. 1986 Feb;82(2):351–359. doi: 10.1016/0041-008x(86)90212-7. [DOI] [PubMed] [Google Scholar]
  18. Higuchi S., Suga M., Dannenberg A. M., Jr, Schofield B. H. Histochemical demonstration of enzyme activities in plastic and paraffin embedded tissue sections. Stain Technol. 1979 Jan;54(1):5–12. doi: 10.3109/10520297909110667. [DOI] [PubMed] [Google Scholar]
  19. Lai W. C., Bennett M., Pakes S. P., Kumar V., Steutermann D., Owusu I., Mikhael A. Resistance to Mycoplasma pulmonis mediated by activated natural killer cells. J Infect Dis. 1990 Jun;161(6):1269–1275. doi: 10.1093/infdis/161.6.1269. [DOI] [PubMed] [Google Scholar]
  20. Lai W. C., Pakes S. P., Lu Y. S., Brayton C. F. Mycoplasma pulmonis infection augments natural killer cell activity in mice. Lab Anim Sci. 1987 Jun;37(3):299–303. [PubMed] [Google Scholar]
  21. Mönkkönen J., Heath T. D. The effects of liposome-encapsulated and free clodronate on the growth of macrophage-like cells in vitro: the role of calcium and iron. Calcif Tissue Int. 1993 Aug;53(2):139–146. doi: 10.1007/BF01321893. [DOI] [PubMed] [Google Scholar]
  22. Parker R. F., Davis J. K., Blalock D. K., Thorp R. B., Simecka J. W., Cassell G. H. Pulmonary clearance of Mycoplasma pulmonis in C57BL/6N and C3H/HeN mice. Infect Immun. 1987 Nov;55(11):2631–2635. doi: 10.1128/iai.55.11.2631-2635.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Parker R. F., Davis J. K., Cassell G. H., White H., Dziedzic D., Blalock D. K., Thorp R. B., Simecka J. W. Short-term exposure to nitrogen dioxide enhances susceptibility to murine respiratory mycoplasmosis and decreases intrapulmonary killing of Mycoplasma pulmonis. Am Rev Respir Dis. 1989 Aug;140(2):502–512. doi: 10.1164/ajrccm/140.2.502. [DOI] [PubMed] [Google Scholar]
  24. Pelorgeas S., Martin J. B., Satre M. Cytotoxicity of dichloromethane diphosphonate and of 1-hydroxyethane-1,1-diphosphonate in the amoebae of the slime mould Dictyostelium discoideum. A 31P NMR study. Biochem Pharmacol. 1992 Dec 1;44(11):2157–2163. doi: 10.1016/0006-2952(92)90342-g. [DOI] [PubMed] [Google Scholar]
  25. Proffitt R. T., Williams L. E., Presant C. A., Tin G. W., Uliana J. A., Gamble R. C., Baldeschwieler J. D. Liposomal blockade of the reticuloendothelial system: improved tumor imaging with small unilamellar vesicles. Science. 1983 Apr 29;220(4596):502–505. doi: 10.1126/science.6836294. [DOI] [PubMed] [Google Scholar]
  26. Qian Q., Jutila M. A., Van Rooijen N., Cutler J. E. Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated candidiasis. J Immunol. 1994 May 15;152(10):5000–5008. [PubMed] [Google Scholar]
  27. Sherwin R. P., Carlson D. A. Protein content of lung lavage fluid of guinea pigs exposed to 0.4 ppm nitrogen dioxide. Arch Environ Health. 1973 Aug;27(2):90–93. doi: 10.1080/00039896.1973.10666325. [DOI] [PubMed] [Google Scholar]
  28. Thepen T., McMenamin C., Oliver J., Kraal G., Holt P. G. Regulation of immune response to inhaled antigen by alveolar macrophages: differential effects of in vivo alveolar macrophage elimination on the induction of tolerance vs. immunity. Eur J Immunol. 1991 Nov;21(11):2845–2850. doi: 10.1002/eji.1830211128. [DOI] [PubMed] [Google Scholar]
  29. Thepen T., Van Rooijen N., Kraal G. Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med. 1989 Aug 1;170(2):499–509. doi: 10.1084/jem.170.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Van Rooijen N., Kors N., vd Ende M., Dijkstra C. D. Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome-encapsulated dichloromethylene diphosphonate. Cell Tissue Res. 1990 May;260(2):215–222. doi: 10.1007/BF00318625. [DOI] [PubMed] [Google Scholar]
  31. Van Rooijen N., Sanders A. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods. 1994 Sep 14;174(1-2):83–93. doi: 10.1016/0022-1759(94)90012-4. [DOI] [PubMed] [Google Scholar]
  32. Van Rooijen N. The liposome-mediated macrophage 'suicide' technique. J Immunol Methods. 1989 Nov 13;124(1):1–6. doi: 10.1016/0022-1759(89)90178-6. [DOI] [PubMed] [Google Scholar]
  33. van Rooijen N., Kors N., Kraal G. Macrophage subset repopulation in the spleen: differential kinetics after liposome-mediated elimination. J Leukoc Biol. 1989 Feb;45(2):97–104. doi: 10.1002/jlb.45.2.97. [DOI] [PubMed] [Google Scholar]
  34. 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]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES