Intratracheal macrophage-activating lipopeptide-2 reduces metastasis in the rat lung

Am J Respir Cell Mol Biol. 2003 Mar;28(3):316-21. doi: 10.1165/rcmb.2002-0106OC.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary*
  • Animals
  • Bacterial Proteins / immunology*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cell Line
  • Fluoresceins
  • Fluorescent Dyes
  • Injections, Intravenous
  • Instillation, Drug
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lipopeptides
  • Lung Neoplasms / immunology
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Monocytes / drug effects
  • Monocytes / immunology
  • Oligopeptides / administration & dosage
  • Oligopeptides / immunology
  • Oligopeptides / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Time Factors
  • Trachea*
  • Tumor Cells, Cultured


  • Bacterial Proteins
  • Fluoresceins
  • Fluorescent Dyes
  • Lipopeptides
  • Oligopeptides
  • macrophage stimulatory lipopeptide 2