MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van de Water, B.
Right arrow Articles by Kuiper, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van de Water, B.
Right arrow Articles by Kuiper, J.

Activation of rat Kupffer cells to tumoricidal cells by the immunomodulator muramyl tripeptide-phosphatidylethanolamine incorporated into the novel drug carrier lactosylated low density lipoprotein

B van de Water, TJ van Berkel and J Kuiper

Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Sylvius Laboratory, The Netherlands.

Lactosylated low density lipoprotein (lac-LDL) is a potential carrier for the site-specific delivery of lipophilic drugs to liver macrophages (Kupffer cells). In the present study we evaluated the application of lac-LDL as a carrier to target the immunomodulator muramyl tripeptide- phosphatidylethanolamine (MTP-PE) to rat Kupffer cells, to specifically activate these cells to tumor-killing cells. The drug carrier 125I- labeled lac-LDL interacted with a galactose-specific recognition system on isolated rat Kupffer cells. The in vitro association of 125I-lac-LDL at 37 degrees was maximal after 20 min, whereas degradation of 125I-lac- LDL was observed after a lag period of 10 min. Cultured rat Kupffer cells were activated after incubation with MTP-PE incorporated into lac- LDL. Lac-LDL-MTP-PE induced a 2-fold increase in the amount of newly synthesized proteins secreted by Kupffer cells. Lac-LDL-MTP-PE induced a concentration-dependent increase in the cytostatic and cytolytic activities of Kupffer cells towards tumor cells (B16F10 melanoma cells) in vitro. Treatment of rats with lac-LDL-MTP-PE also resulted in dose- dependent activation of Kupffer cells to tumoricidal cells, whereas the drug carrier alone had only a minor effect on this activity of Kupffer cells. The present data show that lac-LDL is an effective carrier for the delivery of the lipophilic immunomodulator MTP-PE to rat Kupffer cells. The specific activation of Kupffer cells to tumoricidal cells by lac-LDL-MTP-PE may be beneficial for the treatment of liver metastases.

Volume 45, Issue 5, pp. 971-977, 05/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 RadiologyHome page
J. B. Kruskal, A. Azouz, H. Korideck, M. El-Hallak, S. C. Robson, P. Thomas, and S. N. Goldberg
Hepatic Colorectal Cancer Metastases: Imaging Initial Steps of Formation in Mice
Radiology, June 1, 2007; 243(3): 703 - 711.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics