This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peetermans, W E Articles by van Furth, R Search for Related Content PubMed PubMed Citation Articles by Peetermans, W E Articles by van Furth, R

Murine peritoneal macrophages activated by the mycobacterial 65-kilodalton heat shock protein express enhanced microbicidal activity in vitro.

Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.

ABSTRACT

After an intraperitoneal (i.p.) injection of purified protein derivative, peritoneal macrophages from mice infected with Mycobacterium bovis bacillus Calmette-Guérin (BCG) show an enhanced respiratory burst, inhibit the intracellular proliferation of Toxoplasma gondii, and kill Listeria monocytogenes more efficiently than peritoneal macrophages from normal mice. One of the immunodominant antigens of Mycobacterium spp. is the 65-kDa heat shock protein (Hsp 65), and in the present study, we determined whether injection of this protein into mice leads to activation of their peritoneal macrophages. After an i.p. injection of Hsp 65, peritoneal macrophages from BCG-infected CBA/J mice also released more H2O2, inhibited the proliferation of T. gondii, and killed L. monocytogenes faster than peritoneal macrophages from normal mice, although Hsp 65 was less effective than purified protein derivative. When normal mice were injected with Hsp 65 suspended in saline after a booster injection with Hsp 65, their macrophages did not display enhanced antimicrobial activity, indicating that an adjuvant was required for a cellular immune response against Hsp 65. In the present study, the adjuvant dimethyl dioctadecylammonium bromide (DDA) was preferred because it contains no endotoxin or mycobacterial antigens and because it has been reported that DDA does not induce the production of gamma interferon. Peritoneal macrophages from C57BL/6 and CBA/J mice that had received a subcutaneous injection of Hsp 65 suspended in DDA followed by an i.p. booster injection of Hsp 65 suspended in saline were activated, as indicated by the enhanced production of H2O2, inhibition of the intracellular proliferation of T. gondii, and increased rate of intracellular killing of L. monocytogenes in vitro relative to that by resident peritoneal macrophages and peritoneal macrophages obtained from mice that had received ovalbumin instead of Hsp 65. The rate of phagocytosis of L. monocytogenes was not affected by Hsp 65 treatment. Despite the in vitro expression of enhanced microbicidal activity of peritoneal macrophages, no difference in the growth of L. monocytogenes in the liver and spleen between Hsp 65-treated and control mice was found.

This article has been cited by other articles:

• Hu, Y., Henderson, B., Lund, P. A., Tormay, P., Ahmed, M. T., Gurcha, S. S., Besra, G. S., Coates, A. R. M. (2008). A Mycobacterium tuberculosis Mutant Lacking the groEL Homologue cpn60.1 Is Viable but Fails To Induce an Inflammatory Response in Animal Models of Infection. Infect. Immun. 76: 1535-1546 [Abstract] [Full Text]  
• ROUTSIAS, J. G, TZIOUFAS, A. G (2006). The Role of Chaperone Proteins in Autoimmunity. Ann. N. Y. Acad. Sci. 1088: 52-64 [Abstract] [Full Text]  
• Lewthwaite, J. C., Coates, A. R. M., Tormay, P., Singh, M., Mascagni, P., Poole, S., Roberts, M., Sharp, L., Henderson, B. (2001). Mycobacterium tuberculosis Chaperonin 60.1 Is a More Potent Cytokine Stimulator than Chaperonin 60.2 (Hsp 65) and Contains a CD14-Binding Domain. Infect. Immun. 69: 7349-7355 [Abstract] [Full Text]  
• Chen, W., Syldath, U., Bellmann, K., Burkart, V., Kolb, H. (1999). Human 60-kDa Heat-Shock Protein: A Danger Signal to the Innate Immune System. J. Immunol. 162: 3212-3219 [Abstract] [Full Text]  
• Tabona, P., Reddi, K., Khan, S., Nair, S. P., Crean, St. J. V., Meghji, S., Wilson, M., Preuss, M., Miller, A. D., Poole, S., Carne, S., Henderson, B. (1998). Homogeneous Escherichia coli Chaperonin 60 Induces IL-1{beta} and IL-6 Gene Expression in Human Monocytes by a Mechanism Independent of Protein Conformation. J. Immunol. 161: 1414-1421 [Abstract] [Full Text]