Intratracheal macrophage-activating lipopeptide-2 reduces metastasis in the rat lung.
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.
Shingu
Kiyoshi
K
Department of Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany.
Kruschinski
Carsten
C
Lührmann
Anke
A
Grote
Karsten
K
Tschernig
Thomas
T
Von Hörsten
Stephan
S
Pabst
Reinhard
R
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007275:Injections, Intravenous; D007322:Instillation, Drug; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D055666:Lipopeptides; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014132:Trachea; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D055666:Lipopeptides; D009842:Oligopeptides; C106335:macrophage stimulatory lipopeptide 2