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Intratracheal Macrophage-Activating Lipopeptide-2 Reduces Metastasis in the Rat Lung

Departments of Functional and Applied Anatomy, and of Cardiology and Angiology, Medical School of Hannover, Hannover, Germany

Address correspondence to: Carsten Kruschinski, M.D., Functional and Applied Anatomy 4120, Medical School of Hannover, D-30625 Hannover, Germany. E-mail: Kruschinski.Carsten{at}MH-Hannover.DE

Primary surgery of tumors bears the risk of metastasis to organs such as the lungs. In order to prevent such metastatic processes, in the present study, local intratracheal instillation of macrophage-activating lipopeptide-2 (MALP-2) as a bacterial-derived immunomodulator of cellular host defense responses was performed, and the effects on tumor cell clearance as well as tumor colonization were investigated in the lungs of Fischer 344 (F344) rats. Compared with vehicle controls, local administration of MALP-2 parallel to intravenous inoculation of MADB106 mammary adenocarcinoma tumor cells resulted in a significant reduction of lung colony numbers, whereas MALP-2 application 1 or 3 d afterwards was not effective. Quantification of leukocyte subsets in the lung tissue by immunohistochemistry revealed a significant increase of the number of monocytes in situ, as well as an increased co-localization of Natural Killer (NK) cells with tumor cells. Synthetic MALP-2 is easily available, with virtually no limitation to the amount of compound, and easily applicable by inhalation. Therefore, as local immunostimulative effects of the bacterial antigen MALP-2 have successfully been demonstrated, its use as an immunotherapeutic agent is worth further investigation.

Abbreviations: alkaline phosphatase/anti–alkaline phosphatase, APAAP • 5-(and 6-)carboxyfluorescein diacetate succinimidyl ester, CFSE • Fischer 344 rats, F344 rats • interleukin, IL • macrophage-activating lipopeptide-2, MALP-2 • monocyte chemotactic protein, MCP • macrophage inflammatory protein, MIP • nuclear factor-B, NF-B • Natural Killer, NK • reverse transcriptase–polymerase chain reaction, RT-PCR • Toll-like receptor, TLR

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