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Infection and Immunity, July 2002, p. 3785-3792, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3785-3792.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vivo Effects of a Synthetic 2-Kilodalton Macrophage-Activating Lipopeptide of Mycoplasma fermentans after Pulmonary Application

Anke Lührmann,1* Ursula Deiters,2 Julia Skokowa,3 Michaela Hanke,1 Johannes E. Gessner,3 Peter F. Mühlradt,2 Reinhard Pabst,1 and Thomas Tschernig1

Departments of Functional and Applied Anatomy,1 Clinical Immunology, Medical School of Hannover, 30623 Hannover,,3 Immunobiology Research Group, Gesellschaft für Biotechnologische Forschung mbH, 38124 Braunschweig, Germany2

Received 4 January 2002/ Returned for modification 6 February 2002/ Accepted 3 April 2002

Mycoplasmas can cause interstitial pneumonias inducing critical illness in humans and animals. Mycoplasma infections are characterized by an influx of neutrophils, followed by an accumulation of macrophages and lymphocytes. The present study deals with the question of which mycoplasmal components cause this host reaction. The mycoplasma-derived, macrophage-activating lipopeptide 2S-MALP-2 was used to mimic the sequelae of a mycoplasma infection. To this end, 2S-MALP-2 was intratracheally instilled into the lungs of Lewis rats, and the bronchoalveolar lavage cells were examined at different times after different doses of 2S-MALP-2. Application of 2.5 µg induced a pronounced leukocyte accumulation in the bronchoalveolar space. At 24 h after 2S-MALP-2 administration, the majority of leukocytes consisted of neutrophils, followed by macrophages, peaking on days 2 and 3. Lymphocyte numbers, although amounting to only a few percent of the total bronchoalveolar lavage cells, also increased significantly, with maximal lymphocyte accumulation occurring by 72 h after instillation. The leukocyte count of the lung interstitium was increased on day 3 after treatment. After 10 days all investigated cell populations returned to control levels. Transient chemotactic activity for neutrophils was detected in the bronchoalveolar lavage fluid early after 2S-MALP-2 application, followed by monocyte chemoattractant protein-1 activity (MCP-1) in lung homogenates. MCP-1 was produced by bronchoalveolar lavage cells upon stimulation with 2S-MALP-2. Our data indicate that mycoplasmal lipoproteins and lipopeptides are probably the most relevant mycoplasmal components for the early host reaction. The primary target cells are likely to be the alveolar macrophages liberating chemokines, which attract further leukocytes.

* Corresponding author. Mailing address: Functional and Applied Anatomy 4120, Medical School of Hannover, Carl-Neuberg Str. 1, 30625 Hannover, Germany. Phone: 49-511/532-6740. Fax: 49-511/532-2948. E-mail: luehrmann.anke{at}mh-hannover.de.

Editor: S. H. E. Kaufmann

Infection and Immunity, July 2002, p. 3785-3792, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3785-3792.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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